bluuebunny/crossref_metadata_2025 huggingface dataset:
Allosteric effects of SSB C-terminal tail on assembly ofE. coliRecOR proteins
Authors: Shinn Min Kyung , Kozlov Alexander G , Lohman Timothy M
Published: December 2020

Escherichia coli RecO is a recombination mediator protein that functions in the RecF pathway of homologous recombination, in concert with RecR, and interacts with E. coli single stranded (ss) DNA binding (SSB) protein via the last 9 amino acids of the C-terminal tails (SSB-Ct). Structures of the E. coli RecR and RecOR complexes are unavailable; however, crystal structures from other organisms show differences in RecR oligomeric state and RecO stoichiometry. We report analytical ultracentrifugation studies of E. coli RecR assembly and its interaction with RecO for a range of solution conditions using both sedimentation velocity and equilibrium approaches. We find that RecR exists in a pH-dependent dimer-tetramer equilibrium that explains the different assembly states reported in previous studies. RecO binds with positive cooperativity to a RecR tetramer, forming both RecR4O and RecR4O2 complexes. We find no evidence of a stable RecO complex with RecR dimers. However, binding of RecO to SSB-Ct peptides elicits an allosteric effect, eliminating the positive cooperativity and shifting the equilibrium to favor a RecR4O complex. These studies suggest a mechanism for how SSB binding to RecO influences the distribution of RecOR complexes to facilitate loading of RecA onto SSB coated ssDNA to initiate homologous recombination.
Impaired Performance in Mental Rotation of Hands and Feet and Its Association with Social Cognition in Patients with Complex Regional Pain Syndrome
Authors: Lee Dasom , Choi Soo-Hee , Noh Eunchung , Lee Won Joon , Jang Joon Hwan , Moon Jee Youn , Kang Do-Hyung
Published: December 2020

Objectives. 

So far, dysfunction in mental rotation has been assessed in relation to the left- or right-sided CRPS. Here we examined mental rotation in patients with upper or lower limb CRPS. Considering the potential role of socio-emotional functioning on the perception of body image, we further investigated the association between performance on mental rotation and socio-emotional characteristics.

Methods. 

We examined the performance of 36 patients with upper or lower limb CRPS on the limb laterality recognition. Accuracy and response times for pictures of hands and feet at 4 rotation angles were evaluated. Socio-emotional functioning was measured by the Interpersonal Reactivity Scale and the Toronto Alexithymia Scale.

Results. 

Patients with upper limb pain showed longer RTs to recognize the laterality of hands than feet (P = 0.002), whereas patients with lower limb pain showed longer RTs for feet than hands (P = 0.039). Exploratory correlation analyses revealed that RTs for feet were negatively correlated with the levels of empathic ability to take another’s perspective (P = 0.006) and positively correlated with the level of emotional difficulty in identifying feelings (P = 0.006).

Conclusions. 

This study is the first to report selectively impaired mental rotation of hands vs feet in patients with upper or lower limb CRPS. The findings suggest that impaired mental rotation derives from relative deficits in the representation of the affected limb. Correlations between impaired mental rotation and socio-emotional inability indicate that an altered body schema may be closely associated with impaired social cognitive aspects in CRPS patients.
The Loss of Capacity in Public Organizations: A Public Administration Challenge
Authors: Ansell Christopher K , Comfort Louise , Keller Ann , LaPorte Todd , Schulman Paul
Published: December 2020

Important challenges to the administrative, policy-making, and implementation capacities of public organizations have arisen in recent years. These challenges may arise from many quarters, including budget cuts, organizational reforms, and most ominously, political subterfuge. Although limits on capacity may be familiar to the public organizations that must cope with them, they are less well understood by outside observers. This analytical gap undermines our ability to appraise the policy and constitutional implications of capacity loss. To begin the process of deepening our knowledge of public sector organizational capacities, this essay calls for greater investment in understanding the organizational dynamics associated with capacity loss.
The CHY-Type Zinc Finger Protein FgChy1 Regulates Polarized Growth, Pathogenicity, and Microtubule Assembly in Fusarium graminearum
Authors: Cao Shulin , Li Wei , Li Chaohui , Wang Guanghui , Jiang Wenqiang , Sun Haiyan , Deng Yuanyu , Chen Huaigu
Published: December 2020

Microtubules (MTs), as transport tracks, play important roles in hyphal-tip growth in filamentous fungi, but MT-associated proteins involved in polarized growth remain unknown. Here, we found that one novel zinc finger protein, FgChy1, is required for MT morphology and polarized growth in Fusarium graminearum. The Fgchy1 mutant presented curved and directionless growth of hyphae. Importantly, the conidia and germ tubes of the Fgchy1 mutant exhibited badly damaged and less-organized beta-tubulin cytoskeletons. Compared with the wild type, the Fgchy1 mutant lost the ability to maintain polarity and was also more sensitive to the anti-MT drugs carbendazim and nocodazole, likely due to the impaired MT cytoskeleton. Indeed, the hyphae of the wild type treated with nocodazole exhibited a morphology consistent with that of the Fgchy1 mutant. Interestingly, the disruption of FgChy1 resulted in the off-center localization of actin patches and the polarity-related polarisome protein FgSpa2 from the hyphal-tip axis. A similar defect in FgSpa2 localization was also observed in the nocodazole-treated wild-type strain. In addition, FgChy1 is also required for conidiogenesis, septation, sexual reproduction, pathogenicity, and deoxynivalenol production. Overall, this study provides the first demonstrations of the functions of the novel zinc finger protein FgChy1 in polarized growth, development, and virulence in filamentous fungi.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Complete Chromosome-Scale Genome Sequence Resource forSporisorium panici-leucophaei, the Causal Agent of Sourgrass Smut Disease
Authors: Crestana Gustavo Schiavone , Taniguti Lucas Mitsuo , dos Santos Clesivan Pereira , Benevenuto Juliana , Ceresini Paulo Cezar , Carvalho Giselle , Kitajima João Paulo , Monteiro-Vitorello Claudia Barros
Published: December 2020

Here, we present the first complete chromosome-level genome assembly of the smut fungus strain Sporisorium panici-leucophaei SPL10A, the causal agent of the sourgrass (Digitaria insularis) smut disease. Combining Illumina paired-end and Nanopore long reads, we generated a final assembly composed of 23 chromosomes (22 nuclear and one mitochondrial) with 18,915,934 bp. Gene prediction accomplished using extrinsic evidence from the sugarcane smut fungus Sporisorium scitamineum originated a total of 6,402 protein-encoding genes. The secretome (388 proteins) and the effectorome repertoires (68 candidates) were also predicted, given their crucial roles in plant-pathogen interactions. The complete telomere-to-telomere chromosome sequences of this poorly studied fungus will provide a valuable resource for future comparative genomic studies among smuts to unravel their underlying pathogenicity mechanisms.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Positive Regulatory Domain I–binding Factor 1 Mediates Peripheral Nerve Injury–induced Nociception in Mice by Repressing Kv4.3 Channel Expression
Authors: Wang Cunjin , Pan Yuchen , Zhang Wenwen , Chen Ying , Li Chuhan , Zhao Fang , Behnisch Thomas
Published: December 2020

Background

The transcriptional repressor positive regulatory domain I–binding factor 1 (PRDM1) is expressed in adult mouse dorsal root ganglion and regulates the formation and function of peripheral sensory neurons. The authors hypothesized that PRDM1 in the dorsal root ganglion may contribute to peripheral nerve injury–induced nociception regulation and that its mechanism may involve Kv4.3 channel transcriptional repression.

Methods

Nociception was induced in C57BL/6 mice by applying chronic constriction injury, complete Freund’s adjuvant, or capsaicin plantar injection. Nociceptive response was evaluated by mechanical allodynia, thermal hyperalgesia, cold hyperalgesia, or gait analysis. The role of PRDM1 was evaluated by injection of Prdm1 knockdown and overexpression adeno-associated viruses. The interaction of PRDM1 at the Kv4.3 (Kcnd3) promoter was evaluated by chromatin immunoprecipitation assay. Excitability of dorsal root ganglion neurons was evaluated by whole cell patch clamp recordings, and calcium signaling in spinal dorsal horn neurons was evaluated by in vivo two-photon imaging.

Results

Peripheral nerve injury increased PRDM1 expression in the dorsal root ganglion, which reduced the activity of the Kv4.3 promoter and repressed Kv4.3 channel expression (injured vs. uninjured; all P < 0.001). Knockdown of PRDM1 rescued Kv4.3 expression, reduced the high excitability of injured dorsal root ganglion neurons, and alleviated peripheral nerve injury–induced nociception (short hairpin RNA vs. Scram; all P < 0.05). In contrast, PRDM1 overexpression in naive mouse dorsal root ganglion neurons diminished Kv4.3 channel expression and induced hyperalgesia (PRDM1 overexpression vs. control, mean ± SD; n = 13; all P < 0.0001) as evaluated by mechanical allodynia (0.6 ± 0.3 vs. 1.2 ± 0.2 g), thermal hyperalgesia (5.2 ± 1.3 vs. 9.8 ± 1.7 s), and cold hyperalgesia (3.4 ± 0.5 vs. 5.3 ± 0.6 s). Finally, PRDM1 downregulation in naive mice reduced the calcium signaling response of spinal dorsal horn neurons to thermal stimulation.

Conclusions

PRDM1 contributes to peripheral nerve injury–induced nociception by repressing Kv4.3 channel expression in injured dorsal root ganglion neurons.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
A Novel “Eccentric” Therapeutic Approach for Individuals Recovering From COVID-19
Authors: Gurovich Alvaro N. , Tiwari Sangeeta , Kehl Stephanie , Umucu Emre , Peñailillo Luis
Published: December 2020

Since its appearance in December 2019, COVID-19 has sparked an unprecedented global health care and economic crisis with a fallout predicted to last well into the foreseeable future. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible of COVID-19. The detrimental effects of COVID-19 in the human body have 2 major sources: (1) the infection per se and (2) prolonged bed rest time, which might include hospitalization and even intensive care unit admittance. In addition, the COVID-19 pandemic has altered the mental health status of both healthy and COVID-19 ill persons. It is expected that millions of people will recover from COVID-19; however, their physical and mental health status during recovery might take longer than expected due to the massive inflammation, profound muscle waste, and several unknown consequences, especially in the cardiorespiratory system. Under this perspective, eccentric exercise training might raise as a therapeutic alternative to efficiently improve the physical and mental health status of patients recovering from COVID-19, as previously reported in patients with cancer and chronic pulmonary disease. The purpose of the present clinical perspective is to describe how an eccentric exercise training program might expedite physical and mental recovery in individuals recovering from COVID-19 based on SARS-CoV-2 pathophysiology and evidence-based eccentric exercise training in clinical populations.
Autism Spectrum Disorder Parent Report for Outcome Monitoring: A Preliminary Report of Development and Clinical Utility
Authors: Levin April R. , Baumer Nicole , Amaral Joseph , Sargado Sabrina , Pawlowski Katherine , Chiujdea Madeline , Schmitt Rachel , Weissman Laura , Chan Eugenia , Sideridis Georgios , Bridgemohan Carolyn
Published: December 2020

Objective:

Children with autism spectrum disorder (ASD) face challenges across many functional domains. A tool that gathers relevant clinical information before visits, emphasizing symptoms that are likely to change over development and inform clinical interventions, could improve health care quality, allowing for more patient-centered and efficient care. This study evaluated the clinical utility and preliminary psychometrics of the ASD Parent Report for Outcome Monitoring (ASD-PROM), a web-based measure assessing competence in core features of ASD, along with the breadth of concerns and comorbidities that frequently co-occur with ASD.

Methods:

An interdisciplinary team drafted the ASD-PROM and made iterative revisions based on parent feedback. Parents of 62 children completed the ASD-PROM before their autism-specialty clinical visit, 53 completed the ASD-PROM twice, and 48 completed the Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) concurrently. Parents (n = 25) and clinicians (n = 13) completed postvisit surveys to assess utility (phase 1). The ASD-PROM was then released for general clinical use (phase 2).

Results:

On a Likert scale (1 = very poorly, 10 = very well), parents found that ASD-PROM items described their child's abilities well (median = 8.0; interquartile range [IQR]: 7.0–9.5) and had a positive effect on care (median = 8.0; IQR: 7.0–10.0). Clinicians found the ASD-PROM effective in assessing parent-reported patient abilities (median = 9.0, IQR: 7.0–9.0) and felt the ASD-PROM helped make their care more patient-centered and efficient (both median = 8.0, IQR: 6.0–9.0). Two-week test-retest reliability was acceptable (0.95). ASD-PROM scores correlated positively with scores from similar domains on the Vineland-II (Pearson r 0.30–0.50, medium to large effects).

Conclusion:

The ASD-PROM is a freely available tool to gather information on developmental and behavioral functioning in children with ASD before autism-specialty clinical visits. Clinical utility and preliminary psychometrics are promising, although limitations (including a low response rate during clinical use and a need for additional in-depth assessments and potential resulting modifications to the tool) remain to be addressed. Ultimately, the ASD-PROM may help promote patient-centered and efficient care for children across a wide range of ages and developmental levels.
Associations Between Participation in After-School Activities, Attention-Deficit/Hyperactivity Disorder Severity, and School Functioning
Authors: Lax Yonit , Brown Suzette N. , Silver Michael , Brown Nicole M.
Published: December 2020

Objective:

To examine the association between after-school activity (ASA) participation, attention-deficit/hyperactivity disorder (ADHD) severity, and school functioning among children with ADHD.

Methods:

A cross-sectional study was conducted using data from the 2016 National Survey of Children's Health on ADHD severity, ASAs and 2 domains of school functioning among children with ADHD: missed days from school and calls home from school.

Results:

Of 4,049 children with ADHD (weighted N = 5,010,662), 71.8% participated in at least 1 ASA. In multivariable regression analyses, ASA participation was associated with lower odds of moderate-to-severe ADHD [adjusted odds ratio (aOR): 0.62, 95% confidence interval (CI), 0.46–0.85] and lower odds of missed school days (aOR 0.55, 95% CI, 0.41–0.74). We did not find significant associations with calls home from school (aOR 0.79, 95% CI, 0.59–1.07).

Conclusion:

After-school activity participation is associated with decreased ADHD severity and reduced school absenteeism. Efforts to optimize ADHD outcomes should consider engaging children and adolescents in ASAs.
Perindopril Reduces Arterial Pressure and Does Not Inhibit Exercise-Induced Angiogenesis in Spontaneously Hypertensive Rats
Authors: Miotto Danyelle S. , Duchatsch Francine , Macedo Anderson G. , Ruiz Thalles F.R. , Vicentini Carlos A. , Amaral Sandra L.
Published: December 2020

Sympathetic activity, arteriolar structure, and angiogenesis are important mechanisms modulating hypertension and this study aimed to analyze the effects of perindopril treatment, associated or not with exercise training, on the mechanisms that control blood pressure (BP) in hypertensive rats. Spontaneously hypertensive rats (SHR) were allocated into 4 groups: 1/sedentary (S); 2/perindopril (P, 3.0 mg/kg/d); 3/trained (T); and 4/trained + perindopril (TP). Wistar rats were used as normotensive sedentary control group. SHR were assigned to undergo a treadmill training (T) or were kept sedentary. Heart rate, BP, sympathetic activity to the vessels (LF-SBP), and skeletal muscle and myocardial morphometric analyses were performed. BP was significantly lower after all 3 strategies, compared with S and was accompanied by lower LF-SBP (−76%, −53%, and −44%, for P, T, and TP, respectively). Arteriolar vessel wall cross-sectional area was lower after treatments (−56%, −52%, and −56%, for P, T, and TP, respectively), and only TP presented higher arteriolar lumen area. Capillary rarefaction was present in soleus muscle and myocardium in S group and both trained groups presented higher vessel density, although perindopril attenuated this increase in soleus muscle. Although myocyte diameter was not different between groups, myocardial collagen deposition area, higher in S group, was lower after 3 strategies. In conclusion, we may suggest that perindopril could be an option for the hypertensive people who practice exercise and need a specific pharmacological treatment to reach a better BP control, mainly because training-induced angiogenesis is an important response to facilitate blood flow perfusion and oxygen uptake and perindopril did not attenuate this response.
Skeletal muscle (dys)function in heart failure with preserved ejection fraction
Authors: Saw Eng Leng , Ramachandran Swetha , Valero-Muñoz Maria , Sam Flora
Published: December 2020

Purpose of review

Skeletal muscle dysfunction contributes to exercise intolerance, which manifests as dyspnea and fatiguability in patients with heart failure with preserved ejection fraction (HFpEF). This review aims to summarize the current understanding of skeletal muscle dysfunction in HFpEF.

Recent findings

Animal and human studies in HFpEF provide insights into the pathophysiological alterations in skeletal muscle structure and function with the identification of several molecular mechanisms. Exercise training and novel pharmacological therapies that target skeletal muscle are proposed as therapeutic interventions to treat HFpEF.

There is evidence that skeletal muscle dysfunction plays a pathophysiological role in HFpEF. However, precise mechanistic insights are needed to understand the contribution of skeletal muscle dysfunction in HFpEF.
COVID-19 myocarditis and long-term heart failure sequelae
Authors: Liu Jing , Deswal Anita , Khalid Umair
Published: December 2020

Purpose of review

The clinical syndrome of coronavirus disease 2019 (COVID-19) has become a global pandemic leading to significant morbidity and mortality. Cardiac dysfunction is commonly seen in these patients, often presenting as clinical heart failure. Accordingly, we aim to provide a comprehensive review on COVID-19 myocarditis and its long-term heart failure sequelae.

Recent findings

Several suspected cases of COVID-19 myocarditis have been reported. It is often not clear if the acute myocardial dysfunction is caused by myocarditis or secondary to generalized inflammatory state of cytokine release or microvascular thrombotic angiopathy. Ischemia may also need to be ruled out. Regardless, myocardial dysfunction in these patients is associated with poor overall prognosis. Laboratory testing, echocardiography, cardiac magnetic resonance imaging, and even endomyocardial biopsy may be needed for timely diagnosis. Several treatment strategies have been described, including both supportive and targeted therapies.

COVID-19 can cause a spectrum of ventricular dysfunction ranging from mild disease to fulminant myocarditis with hemodynamic instability. Future research is needed to understand the true prevalence of COVID-19 myocarditis, as well as to better define various diagnostic protocols and treatment strategies.
Pulmonary hypertension in heart failure
Authors: Duran Antonio , Mandras Stacy
Published: December 2020

Purpose of review

Pulmonary hypertension (PH) occurs frequently in heart failure (HF) and confers worse prognosis. It becomes important to adequately identify these patients to optimize treatment. The purpose of this review is to inform about the updated classification of PH in left heart disease, in addition to current and upcoming trials regarding treatment.

Recent findings

The updated classification of PH due to left heart disease now utilizes pulmonary vascular resistance instead of diastolic pulmonary gradient to differentiate between isolated postcapillary and combined pre and postcapillary PH. In regards to treatment, recent clinical trials continue to provide data that pulmonary vasodilators do not improve outcomes in this population.

Management of underlying heart disease and optimal control of comorbidities continues to be the mainstay of treatment in PH due to HF. At this time, current data does not support the use of PH-directed therapies.
REPEATABILITY OF CHOROIDAL VASCULARITY INDEX MEASUREMENTS USING DIRECTIONAL OPTICAL COHERENCE TOMOGRAPHY IMAGES
Authors: Ersoz Mehmet Giray , Kesim Cem , Karslioglu Melisa Zisan , Yildiz-Tas Ayse , Hasanreisoglu Murat , Sahin Afsun
Published: December 2020

Purpose:

To investigate the repeatability of choroidal vascularity index (CVI) measurements in centered and decentered (regarding pupil entry position of the beam) directional subfoveal optical coherence tomography (OCT) scans with (CVI1) and without (CVI2) brightness adjustment.

Methods:

Thirty-two eyes of 32 healthy volunteers were included in this prospective study. First, the fovea was evaluated by a single horizontal enhanced depth imaging OCT scan in a centered direction. Then, the same subfoveal horizontal line was scanned in a decentered direction. The agreement between CVIs obtained from these centered and decentered directional OCT scans was investigated using Bland–Altman analysis and intraclass correlation coefficient.

Results:

Intraclass correlation coefficient between centered and decentered CVI1 was 0.71 (95% CI: 0.48–0.85, P value < 0.001). Intraclass correlation coefficient between centered and decentered CVI2 was 0.73 (95% CI: 0.5–0.86, P value < 0.001). The mean difference between centered and decentered directional measurements for CVI1 and CVI2 were 0.5 and 0.8, respectively.

Conclusion:

There is moderate agreement between CVIs obtained from centered and decentered directional single OCT scans of the same subfoveal area. Studies investigating choroidal vascularity should be standardized by using the same OCT beam direction in all scans.
Acetabular Rim Disorders/Pincer-type Femoroacetabular Impingement and Hip Arthroscopy
Authors: Larson Christopher M. , LaPrade Robert F. , Floyd Edward R. , McGaver Rebecca S. , Bedi Asheesh
Published: December 2020

Femoroacetabular impingement (FAI) can lead to acetabular impaction, chondral injury, and labral pathology secondary to deformities of the proximal femur (CAM-type FAI), acetabulum (pincer-type FAI), or with combined FAI. While the majority of cases are of the combined type, this paper focuses on acetabular overcoverage/pincer-type deformities. Various pincer subtypes include focal anterior overcoverage, global retroversion, global overcoverage/profunda, protrusio, subspine impingement, and os acetabuli/rim fracture variants. A thorough history and physical examination, plain radiographs, magnetic resonance imaging, 3-dimensional computerized tomography, and diagnostic injections can lead to an accurate assessment of pincer-type variants. Appropriately indicated arthroscopic management techniques and pearls for the various pincer subtypes can lead to improved patient-related outcome measures and a high rate of return to athletic activity for the majority of these patients.
Femoral Version in Hip Arthroscopy: Does it Matter?
Authors: Westermann Robert W. , Willey Michael C.
Published: December 2020

Femoral version is extremely variable between patients presenting with femoroacetabular impingement (FAI). Careful and routine measurement of femoral anteversion is essential in comprehensive preoperative planning. In general, low degrees of femoral version can lead to anterior impingement (especially on the subspine and distal medial femoral neck). High degrees of anteversion can be seen in the setting of acetabular dysplasia and can lead to anterior hip instability and or posterior impingement. In this article, the authors will discuss the role of routine femoral version management for optimal outcomes after hip arthroscopy for FAI.
Recent insights into low-density lipoprotein metabolism and therapy
Authors: Pirillo Angela , Catapano Alberico L. , Norata Giuseppe D.
Published: December 2020

Purpose of review

Elevated levels of low-density lipoprotein cholesterol (LDL-C) are causal to atherosclerosis and, thus, the reduction of LDL-C represents a major objective for the prevention of cardiovascular disease. Aim of this review is to provide an overview on novel strategies to lower LDL-C.

Recent findings

Although inhibiting liver cholesterol biosynthesis by statins is used as the main therapeutic approach to increase hepatic LDL-receptor expression and lower plasma cholesterol levels, novel insights into lipid and lipoprotein biology have led to the development of additional lipid-lowering therapies that can be used in combination with or as an alternative to statins in patients with statin-intolerance. New approaches include bempedoic acid, proprotein convertase subtilisin/kexin type 9 inhibitors, and angiopoietin-like protein 3 inhibitors.

In the last decade, several novel therapeutic approaches have been tested and some of them have been approved as lipid-lowering agents. Some drugs are already available in clinical practice, whereas others are at late stages of development.
Energy expenditure and delivery: does the Micawber principle apply during critical illness?
Authors: Frankenfield David C. , Pearson Keith E.
Published: December 2020

Purpose of review

To determine from existing literature if achieving energy balance in critically ill patients improves outcome. Only randomized clinical trials were considered. Furthermore, the intent had to be that energy intake of the treatment group would reach 100% of requirement, and that the requirement was measured and not estimated.

Recent findings

Six studies meeting the above criteria were identified. Truly positive energy balance was rarely achieved in these studies and protein intake was a confounder because it often varied with the energy intake. The two studies in which energy balance came closest to 100% did suggest clinical benefit, but in both of these studies protein intake was also higher in the high-energy intake group.

The question posed cannot be fully answered based on the available literature. There are some signals that the pursuit of energy balance in critically ill patients might be favorable, but significant uncertainty remains.
Pediatric Patients’ and Parents’ Perspectives of Unsedated Transnasal Endoscopy in Eosinophilic Esophagitis
Authors: Scherer Corey , Sosensky Peri , Schulman‐Green Dena , Levy Meredith , Smith Clinton , Friedlander Joel , Koral Alex
Published: December 2020

Background:

Eosinophilic esophagitis is an increasingly common inflammatory disease of the esophagus. Diagnosis and management are based on the histological presence of eosinophils in the esophageal mucosa, often requiring multiple endoscopies with sedation. Unsedated transnasal endoscopy (TNE), an alternative method of assessing the mucosa without the risks of sedation, is now being performed in the pediatric population. This is the first qualitative study on pediatric patients’ and parents’ experiences with TNE.

Objective:

The objective of the study was to describe pediatric patients’ and parents’ experiences of TNE with the goal of refining TNE protocols to improve the clinical experience.

Methods:

We used a qualitative descriptive approach that included in‐depth, semistructured interviews with patients and parents following completion of TNE. Interviews continued until we reached thematic saturation. We analyzed data using qualitative content analysis.

Results:

A total of 21 interviews were completed. We identified 4 themes: Appeal of TNE; Expectations and Preparation for TNE; Tolerance of TNE; and Evaluation of TNE. Perceived positive aspects of TNE were no exposure to intravenous anesthesia; helpful and clear preparation for the procedure with a demonstration video and physician phone call; distraction during TNE with virtual reality goggles and a stress ball; parent able to accompany the patient; and TNE requiring less time than an esophagogastroduodenoscopy. Negative aspects included patient stress before TNE, patient dislike of nasal spray taste and sensation, and discomfort during the TNE procedure.

Conclusion:

The overall perception of TNE among our participants was positive. Study data will allow pediatric gastroenterologists the opportunity to improve both preparation for and comfort during TNE.
Type 2 Immunity and Age Modify Gene Expression of Coronavirus-induced Disease 2019 Receptors in Eosinophilic Gastrointestinal Disorders
Authors: Chiang Austin W.T. , Duong Loan D. , Shoda Tetsuo , Nhu Quan M. , Ruffner Melanie , Hara Takeo , Aaron Bailey , Joplin Erik , Manresa Mario C. , Abonia J. Pablo , Dellon Evan S , Hirano Ikuo , Gonsalves Nirmala , Gupta Sandeep K. , Furuta Glenn T. , Rothenberg Marc E. , Lewis Nathan E. , Muir Amanda B. , Aceves Seema S.
Published: December 2020

Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can lead to coronavirus-induced disease 2019 (COVID-19). The gastrointestinal (GI) tract is now an appreciated portal of infection. SARS-CoV-2 enters host cells via angiotensin-converting enzyme-2 (ACE2) and the serine protease TMPRSS2. Eosinophilic gastrointestinal disorders (EGIDs) are inflammatory conditions caused by chronic type 2 (T2) inflammation. the effects of the T2 atopic inflammatory milieu on SARS-COV-2 viral entry gene expression in the GI tract is poorly understood. We analyzed tissueACE2andTMPRSS2gene expression in pediatric eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), and in normal adult esophagi using publicly available RNA-sequencing datasets. Similar to findings evaluating the airway, there was no difference in tissue ACE2/TMPRSS2 expression in EoE or EG when compared with control non-EoE/EG esophagus/stomach.ACE2gene expression was significantly lower in esophagi from children with or without EoE and from adults with EoE as compared with normal adult esophagi. Type 2 immunity and pediatric age could be protective for infection by SARS-CoV-2 in the gastrointestinal tract because of decreased expression of ACE2.
Intestinal Microbiome in Preterm Infants Influenced by Enteral Iron Dosing
Authors: Ho Thao , Sarkar Anujit , Szalacha Laura , Groer Maureen W.
Published: December 2020

Objectives:

The aim of the study was to compare the intestinal microbiome in very low birth weight (VLBW) infants who received different enteral iron supplementation (EIS) doses.

Study Design:

Longitudinal stool collection in 80 VLBW infants were conducted up to 2 months postnatally in a prospective study. The 16S rRNA regions V4 was used to calculate microbiome compositions and the Piphillin software was used for bacterial functional prediction. Linear mixed effect models and Wilcoxon rank-sum tests were performed to examine the relationships between initial EIS dosage and stool microbiome and bacterial functional potential.

Results:

There were 105 samples collected before and 237 collected after EIS started from infants with birth gestational age and weight of 28.1 ± 2.4 weeks and 1103 ± 210 g, respectively. The average postnatal age at start of EIS was 17.9 ± 6.9 days and the average initial EIS dose was 4.8 ± 1.1 mg · kg−1 · day−1. Infants who were started on ≥6 mg · kg−1 · day−1 had higher abundances of Proteus and Bifidobacterium and a lower alpha diversity than those started on lower doses (P < 0.05). Infants given higher EIS doses had higher bacterial predicted functional potentials for ferroptosis and epithelial invasion after 2 weeks post EIS.

Conclusions:

Higher EIS dosage is linked to higher abundances of Proteus and Bifidobacterium, and a less diverse microbiome and higher predicted potential of bacterial epithelial invasion. These observational findings should be further studied in a randomized study to elucidate the optimal dosage of EIS in VLBW infants.
Effect of Low-Frequency rTMS and Intensive Speech Therapy Treatment on Patients With Nonfluent Aphasia After Stroke
Authors: Bai Guangtao , Jiang Liang , Ma Wenshuai , Meng Pingping , Li Jiang , Wang Yuyang , Wang Qiang
Published: December 2020

Background:

To observe the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on patients with nonfluent aphasia after stroke.

Materials and Methods:

Thirty patients were divided into control, rTMS, and 2 times a day low-frequency rTMS (2rTMS) groups, and all 3 groups had intensive speech therapy (ST). Patients were assessed by western aphasia battery (WAB) scale. The spontaneous language, listening comprehension, retelling, and naming were scored, respectively. The expression of brain-derived neurotrophic factor (BDNF) in peripheral blood was detected by enzyme-linked immunosorbent assay.

Results:

There was significant difference in aphasia quotient after treatment in the 3 groups. The values of the 4 dimensions in the WAB score of the rTMS group were higher than those in the control group. The WAB scores in the 2rTMS group were higher than those in the rTMS group. After 2 weeks treatment, the BDNF levels in the rTMS group and the 2rTMS group were significantly higher than those in the control group. Four weeks later, the 2rTMS group was significantly increased compared with the control group and the rTMS group.

Conclusions:

Low-frequency rTMS combined with conventional ST treatment can effectively improve the language function of patients with nonfluent aphasia after stroke. Two times a day low-frequency rTMS therapy combined with conventional ST treatment can improve the language function of patients with nonfluent aphasia after stroke more effectively and it also promote the expression of BDNF more effectively, thereby improving nerve repair and protecting brain tissue.
Diagnostic Accuracy of the INSHI Consensus Case Definition for the Diagnosis of Paradoxical Tuberculosis-IRIS
Authors: Stek Cari , Buyze Jozefien , Menten Joris , Schutz Charlotte , Thienemann Friedrich , Blumenthal Lisette , Maartens Gary , Boyles Tom , Wilkinson Robert J. , Meintjes Graeme , Lynen Lutgarde
Published: December 2020

Background:

The diagnosis of paradoxical tuberculosis–associated immune reconstitution inflammatory syndrome (TB-IRIS) relies on characteristic clinical features synthesized as the International Network for the Study of HIV-associated IRIS (INSHI) case definition. There is no confirmatory laboratory test.

Setting:

Site B HIV-TB clinic in Khayelitsha, Cape Town, South Africa.

Methods:

Using data of participants with HIV-associated tuberculosis starting antiretroviral treatment from a prospective trial evaluating prednisone for TB-IRIS prevention, we applied latent class analysis to model a gold standard for TB-IRIS. The model-predicted probability of TB-IRIS for each participant was used to assess the performance of the INSHI case definition and compare its diagnostic accuracy with several adapted case definitions.

Results:

Data for this analysis were complete for 217 participants; 41% developed TB-IRIS. Our latent class model included the following parameters: respiratory symptoms; night sweats; INSHI major criteria 1, 2, and 4; maximum C-reactive protein >90 mg/L; maximum heart rate >120/min; maximum temperature >37.7°C; and preantiretroviral therapy CD4 count <50 cells/µL. The model estimated a TB-IRIS incidence of 43% and had optimal goodness of fit (χ2 = 337, P = 1.0). The INSHI case definition displayed a sensitivity of 0.77 and a specificity of 0.86. Replacing all the minor INSHI criteria with objectives measures (C-reactive protein elevation, fever, and/or tachycardia) resulted in a definition with better diagnostic accuracy, with a sensitivity of 0.89 and a specificity of 0.88.

Conclusion:

The INSHI case definition identifies TB-IRIS with reasonable accuracy. Amending the case definition by replacing INSHI minor criteria with objective variables improved sensitivity without loss of specificity.
The Effect of Mycophenolate Mofetil as First-Line Therapy on the Timing of Urine Protein–to–Creatinine Ratio Reduction in Immunosuppressant-Naive Patients With Lupus Nephritis at a Single Center
Authors: Timlin Homa , Hardenbergh Dylan , Fine Derek , Monroy-Trujillo Jose Manuel , Haque Uzma , Adler Brittany , Vaidya Dhananjay , Geetha Duvuru
Published: December 2020

Background/Objectives

Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis (LN). The purpose of this study was to assess the effect of mycophenolate mofetil (MMF) on the timing of urine protein–to–creatinine ratio reaching 200 mg or less after starting MMF as initial therapy for class III, IV, or V in immunosuppressant-naive patients with LN.

Methods

Patients who had a diagnosis of biopsy-proven LN were included in this cohort study. The initial dose of MMF was 1000 mg twice daily. If no improvement, it was increased to 1500 mg twice daily after 1 month. For statistical analysis, exact binomial distribution 95% confidence intervals were calculated.

Results

Nine patients were identified. There were 3 patients with class III, 3 with class IV, 1 with class III to V, 1 with class II to V, and 1 with class V lupus nephritis. The majority were African Americans (70%). At baseline, proteinuria ranged between 0.41 and 4 g, and 88% had normal estimated glomerular filtration rate. Forty-four percent of patients reached 0.28 g of proteinuria within 8 weeks of starting MMF (95% confidence interval, 14%–79%), all of which maintained the same level of response and normal estimated glomerular filtration rate at 12 months. Thirty-three percent of patients achieved the American College of Rheumatology complete response at 8 weeks.

Conclusions

This study demonstrates that only a minority of immunosuppressant-naive LN patients achieved the American College of Rheumatology complete response at 8 weeks after initiation of MMF. A rapid decline in the proteinuria to 0.28 g within the first 8 weeks of the treatment correlated strongly with achieving the same level of response at 12 months.
The Impact of Biologic Drugs on High-Density Lipoprotein Cholesterol Efflux Capacity in Rheumatoid Arthritis Patients
Authors: Cacciapaglia Fabio , Perniola Simone , Venerito Vincenzo , Anelli Maria Grazia , Härdfeldt Jennifer , Fornaro Marco , Moschetta Antonio , Iannone Florenzo
Published: December 2020

Background

One of the most intriguing conundrums in patients with rheumatoid arthritis (RA) is the lack of correlation between cholesterol levels and cardiovascular (CV) events, diminishing the reliability of plasmatic lipid levels in estimating the CV risk. High-density lipoprotein cholesterol efflux capacity (HDLc-EC) directly indicates the functional ability of HDL to scavenge cholesterol from vascular wall and may provide better information on the atherogenic risk. The aim of this study was to examine the effects of different disease-modifying antirheumatic drugs on HDLc-EC in RA.

Methods

Consecutive RA patients treated with different biologic disease-modifying antirheumatic drugs or methotrexate monotherapy were longitudinally observed. Demographic and clinical features as well as lipid profile were recorded at baseline, 24-week, and 52-week follow-up. At the same time points, HDLc-EC was evaluated using J771 macrophages and a fluorometric assay.

Results

We analyzed 100 RA patients on methotrexate, infliximab, tocilizumab, abatacept, or rituximab. No significant changes in the lipoprotein levels were detected, whereas the mean HDLc-EC statistically increased from baseline (22.5% ± 4.8%) to 24 weeks (24.5% ± 5.7%; p < 0.001) and 52 weeks (25.1% ± 5.9%; p < 0.001). Patients on tocilizumab showed the highest increase in HDLc-EC, already at 24 weeks. Patients on treatment with infliximab or rituximab showed a significant increase in HDLc-EC at 52 weeks. No significant changes were detected in abatacept and methotrexate groups.

Conclusions

Some treatments may impact cholesterol reverse transport in RA. The improved HDLc-EC, independently from lipid levels, may be one of the missing links between inflammation, lipids, and CV risk in RA.
First Biologic Drug Persistence in Patients With Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis
Authors: Ngo Minh-Duc , Zummer Michel , Andersen Kathleen M. , Richard Nicolas
Published: December 2020

Background/Objectives

Axial spondyloarthritis (axSpA) includes ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA). Both are managed with biologic therapies; however, there is a lack of evidence for nr-axSpA therapies. The primary objective was to compare persistence to first biologic between AS and nr-axSpA patients in a longitudinal cohort. Secondary objectives were to examine disease activity markers over time and to evaluate predictors for drug discontinuation.

Methods

Data were obtained from persons enrolled in the SpondyloArthritis Research Consortium of Canada registry between 2003 and 2018. Kaplan-Meier curves were constructed from the time of biologic initiation until discontinuation and compared using the log-rank test. Subanalyses were performed according to calendar year and disease activity. Cox proportional hazards models were used to identify factors associated with discontinuation.

Results

We identified 385 biologic-naive persons. Overall, the 349 AS participants had longer persistence to their first biologic than the 36 nr-axSpA subjects (p < 0.01). The Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index decreased by 2.3 points (95% confidence interval [CI], 1.9–2.7) and 3.2 points (95% CI, 2.6–3.7), respectively, in the first year and were stable thereafter. Adjusting for sex, human leukocyte antigen B27, and smoking status, nr-axSpA patients were more likely to discontinue their biologic than AS patients (hazards ratio, 1.65; 95% CI, 1.03–2.62).

Conclusions

In this real-world study, AS patients had longer persistence to their first biologic compared with nr-axSpA, with disease subtype being the most significant predictor of treatment persistence. Future studies should be targeted at assessing long-term clinical outcome of axSpA in the real-world setting.
Can an Artificial Intelligence Decision Aid Decrease False-Positive Breast Biopsies?
Authors: Heller Samantha L. , Wegener Melanie , Babb James S. , Gao Yiming
Published: December 2020

This study aimed to evaluate the effect of an artificial intelligence (AI) support system on breast ultrasound diagnostic accuracy.

In this Health Insurance Portability and Accountability Act–compliant, institutional review board–approved retrospective study, 200 lesions (155 benign, 45 malignant) were randomly selected from consecutive ultrasound-guided biopsies (June 2017–January 2019). Two readers, blinded to clinical history and pathology, evaluated lesions with and without an Food and Drug Administration–approved AI software. Lesion features, Breast Imaging Reporting and Data System (BI-RADS) rating (1–5), reader confidence level (1–5), and AI BI-RADS equivalent (1–5) were recorded. Statistical analysis was performed for diagnostic accuracy, negative predictive value, positive predictive value (PPV), sensitivity, and specificity of reader versus AI BI-RADS. Generalized estimating equation analysis was used for reader versus AI accuracy regarding lesion features and AI impact on low-confidence score lesions. Artificial intelligence effect on false-positive biopsy rate was determined. Statistical tests were conducted at a 2-sided 5% significance level.

There was no significant difference in accuracy (73 vs 69.8%), negative predictive value (100% vs 98.5%), PPV (45.5 vs 42.4%), sensitivity (100% vs 96.7%), and specificity (65.2 vs 61.9; P = 0.118–0.409) for AI versus pooled reader assessment. Artificial intelligence was more accurate than readers for irregular shape (74.1% vs 57.4%, P = 0.002) and less accurate for round shape (26.5% vs 50.0%, P = 0.049). Artificial intelligence improved diagnostic accuracy for reader-rated low-confidence lesions with increased PPV (24.7% AI vs 19.3%, P = 0.004) and specificity (57.8% vs 44.6%, P = 0.008).

Artificial intelligence decision support aid may help improve sonographic diagnostic accuracy, particularly in cases with low reader confidence, thereby decreasing false-positives.
Is it Safe to Be Transplanted From Living Donors Who Recovered From COVID-19? Experience of 31 Kidney Transplants in a Multicenter Cohort Study From India
Authors: Kute Vivek B. , Godara Suraj , Guleria Sandeep , Ray Deepak S. , Aziz Feroz , Hegde Umapati , Sharma Ashish , Nayak K.S. , Siddini Vishwanath , Sarkar Piyali , Thukral Sharmila , Mondal Rabi Ranjan Sow , Goswami Jitendra , Patel Himanshu V. , Abraham M. Abi , Pathak Vivek , Anandh Urmila , Jha Pranaw Kumar , Bavikar Suhas , Bonu Ravi Shankar , Gulati Sanjeev , B.T. Anil Kumar , Yadav Dinesh Kumar
Published: December 2020

Background.

There is lack of data on feasibility and safety of kidney transplants from living donors who recovered from COVID-19.

Methods.

Here, we present a retrospective cohort study of 31 kidney transplant recipients (KTR) from living donors who recovered from polymerase chain reaction confirmed COVID-19 across 19 transplant centers in India from July 3, 2020, to December 5, 2020. We detailed demographics, clinical manifestations, immunosuppression regimen, treatment, and outcomes. Donors with a previous diagnosis of COVID-19 were accepted after documenting 2 negative polymerase chain reaction tests with complete symptom resolution for at least 28 days and significant social distancing for 14 days before surgery.

Results.

COVID-19 clinical severity in donors ranged from completely asymptomatic (71%, n = 22) to mild infection (29%, n = 9). None progressed to moderate or severe stages of the disease in the entire clinical course of home treatment. Patient and graft survival was 100%, respectively, with acute cellular rejection being reported in 6.4% (n = 2) recipient. All recipients and donors were asymptomatic with normal creatinine at median follow-up of 44 days after surgery without any complications relating to surgery and COVID-19.

Conclusions.

Our data support safety of proceeding with living donation for asymptomatic individuals with comprehensive donor, recipients screening before surgery, using a combination of clinical, radiologic, and laboratory criteria. It could provide new insights into the management of KTR from living donors who have recovered from COVID-19 in India. To the best of our knowledge, this remains the largest cohort of KTR from living donors who recovered from COVID-19.