bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic rate dependent exit block after pulmonary vein isolation
Authors: Makker Parth , Dulmovits Eric , Beldner Stuart
Published: March 2021

Rate dependent exit block across the pulmonary veins has been previously described immediately following catheter ablation. We report a case of rate dependent pulmonary vein exit block seen at repeat ablation 7 years after the index procedure. To our knowledge, this is the first report of chronic rate dependent exit block discovered years after circumferential pulmonary vein antral isolation.
Optimization microwave‐assisted extraction of anthocyanins from cranberry using response surface methodology coupled with genetic algorithm and kinetics model analysis
Authors: Xue Hongkun , Tan Jiaqi , Fan Linlin , Li Qian , Cai Xu
Published: March 2021

Cranberry contains abundant anthocyanins. In this study, the extraction process for the microwave‐assisted extraction (MAE) of anthocyanins from cranberry was optimized using response surface methodology coupled with genetic algorithm. The optimum extraction parameters to achieve the highest yield of anthocyanins (3.06 ± 0.05) mg/g from cranberry via MAE was obtained at extraction temperature of 50°C, extraction time of 8 s, ethanol concentration of 52% and solid‐to‐liquid ratio of 1:28 g/ml. The kinetic model of anthocyanins extraction from cranberry was established by plate model based on Fick's first Law, and the key model parameters (extraction rate constant and activation energy) were solved through the experimental results fitting. Results showed that the extraction rate constant increased significantly with the increase of extraction temperature. The activation energy of MAE anthocyanins from cranberry was 27.63 kJ/mol. The results indicated that the MAE process of anthocyanins was endothermic and controlled by mixing reaction and diffusion mechanism. The results provide a basis for industrial scale‐up and in‐depth study of anthocyanins in cranberry.

Practical Applications

Anthocyanins are widely used as food colorants, antioxidants, and anticancer agents. Cranberry is rich in anthocyanins and can be used as a vital source of anthocyanins extraction. In this study, the extraction process for the microwave‐assisted extraction (MAE) of anthocyanins from cranberry was optimized using response surface methodology coupled with genetic algorithm to achieve of maximum anthocyanin yield, and the kinetic model of anthocyanins extraction from cranberry was established by plate model based on Fick's first Law, and the key model parameters (extraction rate constant and activation energy) were solved through the experimental results fitting.
Multicomponent behavioral intervention to reduce exposure to anticholinergics in primary care older adults
Authors: Campbell Noll L. , Holden Richard J. , Tang Qing , Boustani Malaz A. , Teal Evgenia , Hillstrom Jennifer , Tu Wanzhu , Clark Daniel O. , Callahan Christopher M.
Published: March 2021

Objective

To test the impact of a multicomponent behavioral intervention to reduce the use of high‐risk anticholinergic medications in primary care older adults.

Design

Cluster‐randomized controlled trial.

Setting and Participants

Ten primary care clinics within Eskenazi Health in Indianapolis.

Intervention

The multicomponent intervention included provider‐ and patient‐focused components. The provider‐focused component was computerized decision support alerting of the presence of a high‐risk anticholinergic and offering dose‐ and indication‐specific alternatives. The patient‐focused component was a story‐based video providing education and modeling an interaction with a healthcare provider resulting in a medication change. Alerts within the medical record triggered staff to play the video for a patient. Our design intended for parallel, independent priming of both providers and patients immediately before an outpatient face‐to‐face interaction.

Measurement

Medication orders were extracted from the electronic medical record system to evaluate the prescribing behavior and population prevalence of anticholinergic users. The intervention was introduced April 1, 2019, through March 31, 2020, and a preintervention observational period of April 1, 2018, through March 31, 2019, facilitated difference in difference comparisons.

Results

A total of 552 older adults had visits at primary care sites during the study period, with mean age of 72.1 (SD 6.4) years and 45.3% African American. Of the 259 provider‐focused alerts, only three (1.2%) led to a medication change. Of the 276 staff alerts, 4.7% were confirmed to activate the patient‐focused intervention. The intervention resulted in no significant differences in either the number of discontinue orders for anticholinergics (intervention: two additional orders; control: five fewer orders, p = 0.7334) or proportion of the population using anticholinergics following the intervention (preintervention: 6.2% and postintervention: 5.1%, p = 0.6326).

Conclusion

This multicomponent intervention did not reduce the use of high‐risk anticholinergics in older adults receiving primary care. Improving nudges or a policy‐focused component may be necessary to reduce use of high‐risk medications.
Retrospective analysis of a pilot pharmacist‐led hospice deprescribing program initiative
Authors: Le Vy , Patel Neerali , Nguyen Quyen , Woldu Henock , Nguyen Lily , Lee Ava , Deguzman Lynn , Krishnaswami Ashok
Published: March 2021

Context

Medication deprescribing in palliative care settings has been insufficiently studied.

Objective

To determine the feasibility of a deprescribing program in hospice patients with limited life expectancy.

Design

Pharmacist‐led, single arm, single‐centered, retrospective analysis of a pilot deprescribing program in an integrated healthcare delivery organization between 9/1/2018 to 1/31/2019.

Outcome measures

The primary outcome was the proportion of patients who achieved ≥50% reduction of the recommended medications to deprescribe.

Results

A total of 97 patients were included in the analysis. The average age was 77.5 ± 23.7 years, with 53.6% being women and 54.6% white. The most common primary diagnosis was cancer (58.8%), with cardiovascular disease the next most common (15.5%). The mean number of baseline comorbidities was 2.0 ± 1.6. Of 698 prescriptions at the start of hospice enrollment, 79.4% of patients achieved a ≥50% reduction in medications recommended for deprescribing. This success was seen mostly in cardiovascular and other nonspecific medications. We found that every 1‐unit increase in the number of patient encounters with hospice pharmacists was associated with a 3.2‐fold higher odds of achieving a ≥50% reduction in medications that were recommended for deprescribing.

Conclusion

The findings from this pilot study revealed that a collaborative, pharmacist‐led, collaborative medication deprescribing program initiative was associated with a 79% success in ≥50% medication reduction. More frequent patient encounters had higher odds of success. Future studies, utilizing a control group, should focus on determining the effectiveness of the program and the impact on quality of life.
Infidelity treatment from an integrative behavioral couple therapy perspective: Explanatory model and intervention strategies
Authors: Barraca Jorge , Polanski Thomas X.
Published: March 2021

Infidelity has a devastating effect on relationships and is a common reason for seeking couple therapy. However, few empirical studies have demonstrated effective models or strategies for treating this issue. An exception is integrative behavioral couple therapy (IBCT). Nevertheless, IBCT's specific contributions to this therapeutic problem have not been the main focus of any publication. This article briefly mentions the effects that infidelity has on intimate partner relationships and presents the empirical evidence for IBCT's utility in treating affairs. It places special focus on exploring infidelity using IBCT's explanatory model. The application of various IBCT strategies and techniques in infidelity cases is explained both in general and with concrete examples. Whether couple therapy in cases of infidelity should focus specifically on the affair or on a wider scope of issues is discussed, as well as new directions for infidelity research within an IBCT framework.
Pathogenic MAPT mutations Q336H and Q336R have isoform‐dependent differences in aggregation propensity and microtubule dysfunction
Authors: Xia Yuxing , Nasif Lith , Giasson Benoit I.
Published: March 2021

Tauopathies are a group of heterogeneous neurodegenerative disorders characterized by brain deposition of tau inclusions. These insidious disorders include Alzheimer's disease and frontotemporal dementia, the two leading causes of dementia. Mutations in the microtubule‐associated protein tau (MAPT) gene lead to familial forms of frontotemporal dementia. Previously, we used cell‐based assays to screen over 20 missense tau mutations and found that decreased microtubule (MT) binding affinity was the most shared property. As a break from this trend, the MAPT mutations Q336H and Q336R are thought to promote MT assembly rather than inhibit it based on in vitro studies. Q336H and Q336R MAPT mutations also cause early onset frontotemporal dementia with Pick bodies, which are mostly composed of 3R tau isoforms. To provide further insights on the pathobiology of these mutations, we assessed Q336H and Q336R tau mutants for aggregation propensity and MT binding in cell‐based assays in the context of both 0N3R and 0N4R tau isoforms. Q336R tau was prone to prion‐like seeded aggregation but both Q336H and Q336R tau led to increased MT binding. Additionally, we found that different tau isoforms with these mutations heterogeneously regulate different MT subpopulations of tyrosinated and acetylated MTs, markers of newly formed MTs and stable MTs. The Q336H and Q336R tau mutations may exemplify an alternative mechanism where pathogenic tau can bind MTs with higher affinity and hyperstabilize MTs, which prevent proper MT regulation and homeostasis.

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Volumization of the young and the old temple using a highly cross‐linked HA filler
Authors: Müller Daniel S. , Prinz Valentina , Sulovsky Monika , Cajkovsky Mia , Cotofana Sebastian , Frank Konstantin
Published: March 2021

Background

A plethora of age‐related changes contribute to hollowing of the temples, as bone remodeling, atrophy of the temporalis muscle, thinning of the skin, and deflation of the subcutaneous and deep temporal fat create the appearance of a skeletonized face. In addition, previous studies have established a relationship between facial skeletonization, temporal hollowing, and postmenopausal sarcopenia.

Objective

To compare the volume change, adverse events, and patient satisfaction of soft‐tissue filler injections in the temple between young (<51) and old (>51) females.

Material and Methods

A total of 30 women with a mean age of 53.1 ± 12.1 years underwent bilateral temporal volumization. Adverse events and satisfaction were assessed after 3 and 6 months. 3‐Dimensional surface imaging was performed at baseline and after 2 weeks, 3 and 6 months to assess volumetric changes.

Results

A mean volume of 5.55 ± 1.9 cc was injected into the temples. A total of 31 adverse events were observed in 13 patients. The overall satisfaction of the procedure was very high after 3 and 6 months in both patient groups, and raters showed a significant agreement in their assessment of the aesthetic improvement, while the self‐reported patient satisfaction was also substantially high. The surface‐volume coefficient differed significantly between 14 days and 3 months post‐injection only in pre‐menopausal patients, while no significant difference was detected between 3 and 6 months.

Conclusion

Temporal soft‐tissue filler injections are safe and provide long‐lasting aesthetic improvement both in pre‐ and postmenopausal women.
Effects of excessive dietary zinc or zinc/cadmium and tapeworm infection on the biochemical parameters in rats
Authors: Sloup Vladislav , Jankovská Ivana , Štolcová Magdalena , Magdálek Jan , Karešová Veronika , Lanková Sylva , Langrová Iva
Published: March 2021

The main objective of this study was to determine which biochemical blood parameters can serve as indicators of Zn or Zn/Cd burden and tapeworm infection. This study was performed on 44 Wistar male rats during a 6‐week period, when rats were or were not fed a zinc/cadmium rich diet and were or were not infected with tapeworms (Hymenolepis diminuta). Total protein, albumin, urea, glucose, triacylglycerols, non‐esterified fatty acids, cholesterol, alkaline phosphatase, aspartate aminotransferase, uric acid, Mg, Ca, P and Zn levels were analysed. Control rats with tapeworm infection had significantly higher (p ≤ 0.05) total protein, urea and phosphorus concentrations than did rats unaffected by any experimental factor. Rats given overdoses of zinc lactate exhibited significantly lower glucose levels than did the other rats, especially those infected with tapeworms. Low glucose level in uninfected rats indicate a Zn overdose; high doses of zinc lactate likely decrease levels of glucose via cortisol, which is released during stress. Rats fed the Zn/Cd hyperaccumulating plant Arabidopsis halleri and infected with tapeworms had significantly higher (p ≤ 0.01) cholesterol and urea levels but lower zinc, triacylglycerol, and alkaline phosphatase levels than did rats fed the same diet but free of tapeworms. The increase of alkaline phosphatase level in uninfected rats may indicate both Zn/Cd burden and rat liver damage. Overall, this study not only supports the theory that H. diminuta can serve as a promising model for helminth therapy of the host mammal but also confirmed that this tapeworm is capable to protect somehow the host organism from the harmful effects of heavy metals.
Expression of the PEPT1, CAT, SOD2 and GPX1 genes in the zebrafish intestine supplemented with methionine dipeptide under predation risk
Authors: Casetta Jaísa , Ribeiro Ricardo Pereira , Lewandowski Vanessa , Khatlab Angélica de Souza , de Oliveira Neto Adhemar Rodrigues , Boscolo Wilson Rogério , Gasparino Eliane
Published: March 2021

This study evaluated the effect of methionine supplementation, predation risk and their interaction on gut histology, whole‐body cortisol levels, and intestinal gene expression in zebrafish. A total of 360 one‐year‐old animals were maintained under two environmental conditions and fed diets containing different methionine sources. Fish were fed either a control diet (CTL, without methionine supplementation), a diet supplemented with dl‐methionine (DLM), or a diet supplemented with methionine dipeptide (MM) in the absence (AP) of a predator or in the presence of the predator (PP) for 48 h or 20 days. Predator‐induced stress for 20 days resulted in lower body weight. Zebrafish fed methionine‐supplemented diets had higher weight gain than control fish. We found no effect of predation stress or methionine supplementation on cortisol level. Predation risk and methionine supplementation showed no interaction effect on dipeptide transporter gene expression. After 48 h of predation pressure, zebrafish had higher mRNA expression of SOD2, CAT and GPX1 in the gut. After 20 days of exposure to the predator, zebrafish fed methionine‐supplemented diets had lower expression of GPX1, SOD2 and CAT than those diet CTL. Methionine dipeptide and free methionine supplementation improved growth, intestinal health and survivability of zebrafish both conditions.
Utilization of pelleted and extruded feed by blunt snout bream Megalobrama amblycephala: Insights from growth performance, health status and feed cost
Authors: He Chao‐Fan , Liu Wen‐Bin , Shi Hua‐Juan , Zhang Li , Zhang Ling , Li Xiang‐Fei
Published: March 2021

The present study was conducted to evaluate the utilization of both pelleted feed (PF) and extruded feed (EF) by blunt snout bream Megalobrama amblycephala based on growth performance, stress responses, innate immunity and disease resistance. Both the PF and EF were prepared with the same formula. Fish were divided randomly into 2 groups, including one fed the PF continuously and one offered the EF continuously. The whole feeding trial lasted 8 weeks, after which fish were subjected to Aeromonas hydrophila infection. The results showed that the feed intake, feed conversion ratio, hepatic total superoxide dismutase activity and glutathione content, plasma complement 3 and complement 4 levels as well as myeloperoxidase activity of the EF group were all significantly lower than those of the PF group, while the opposite was true for the condition factor, the viscera index, the abdominal fat percentage, nitrogen and energy retention, hepatic malondialdehyde content, plasma levels of cortisol, glucose, lactate, total protein and globulin as well as the activities of plasma alanine aminotransferase and aspartate aminotransferase. In addition, the EF group also obtained relatively low activities of hepatic glutathione peroxidase and plasma acid phosphatase as well as high cumulative mortality rates at 24–96 h after Aeromonas hydrophila challenge. Furthermore, the feed cost of culturing this species with EF is lower than that with PF. These findings indicated that compared with PF, EF could increase the feed utilization and economic benefits of blunt snout bream, but reduce its anti‐stress ability, non‐specific immunity, A. hydrophila resistance and feed cost.
Composition of woody plant communities drives macrofungal community composition in three climatic regions
Authors: Li Huili , Guo Jiayu , Ye Lei , Gui Heng , Hyde Kevin David , Xu Jianchu , Mortimer Peter Edward
Published: March 2021

Questions

Macrofungi provide important ecosystem functions and economic value. However, their distributive patterns among woody plant communities and the influence of abiotic factors remain poorly understood. We hypothesized that: (a) the community composition and richness of woody plants are significantly positively correlated with macrofungal community composition and species richness; and (b) in addition to plant effects, abiotic factors (geography and climate) contribute significantly to the variability within macrofungal communities.

Location

Northwest (Zhongdian County), west (Baoshan City) and southwest (Xishuangbanna Autonomous Prefecture) Yunnan Province, China.

Methods

We investigated macrofungi, woody plants and abiotic factors at 30 plots across three climate types in Yunnan Province, China. We assessed the distributive patterns and driving factors of macrofungal communities in temperate, subtropical and tropical regions.

Results

Macrofungal species richness did not significantly increase alongside woody plant species richness, while dissimilarities in macrofungal community compositions across the three climatic regions correlated significantly with woody plant communities, elevation, mean annual precipitation, mean annual temperature, longitude and latitude. Variation partitioning analysis indicated that variations in macrofungal community compositions were explicable by woody plant community composition, as well as by spatial and climatic factors. The Mantel test further revealed that woody plant functional groups shaped macrofungal functional groups. These results indicate that the distribution of macrofungi at the regional scale is mainly affected by woody plant communities, followed by spatial and climatic factors in the three climatic regions.

Conclusions

We concluded that dominant woody plant species could be used as indicators of macrofungal community compositions. Accordingly, applying knowledge on the dominant woody plant communities into forest management schemes could be an effective strategy for supporting macrofungal conservation.
Diversity and abundance of soil microbial communities decline, and community compositions change with severity of post‐logging fire
Authors: Ammitzboll Hans , Jordan Gregory J. , Baker Susan C. , Freeman Jules , Bissett Andrew
Published: March 2021

Understanding the effects of logging and fire on forest soil communities is integral to our knowledge of forest ecology and effective resource management. The resulting changes in soil biota have substantial impacts on forest succession and associated ecosystem processes. We quantified bacterial and fungal abundance, diversity and community composition across a logging and burn severity gradient, approximately one month after fire, in temperate wet eucalypt forests in Tasmania, Australia. Using amplicon sequencing and real‐time quantitative PCR of the bacterial 16S rRNA gene and fungal ITS1 region, we demonstrate that (i) burn severity is a strong driver of soil microbial community composition, (ii) logging and high severity burning substantially reduce the biomass and diversity of soil bacteria and fungi, and (iii) the impacts of logging and burning on soil microbial communities are largely restricted to the top 10 cm of soil, with weak impacts on the subsoil. The impacts of disturbance on microbial community composition are greater than the effects of site‐to‐site edaphic differences. Fire also drives more divergence in community composition than logging alone. Key microbial taxa driving differences in severely burnt soils include bacterial genera implicated in plant‐growth promotion and producing antifungal compounds as well as saprotrophic fungi that are also capable of forming ectomycorrhizal associations. Our research suggests that low‐moderate severity burns are important for maintaining diversity and biomass in soil microbial communities but having a range of burn severities across a site contributes to the overall diversity of habitat conditions providing for both microbial and plant diversity.
Social isolation causes downregulation of immune and stress response genes and behavioural changes in a social insect
Authors: Scharf Inon , Stoldt Marah , Libbrecht Romain , Höpfner Anna Lena , Jongepier Evelien , Kever Marion , Foitzik Susanne
Published: March 2021

Humans and other social mammals experience isolation from their group as stressful, triggering behavioural and physiological anomalies that reduce fitness. While social isolation has been intensely studied in social mammals, it is less clear how social insects, which evolved sociality independently, respond to isolation. Here we examined whether the typical mammalian responses to social isolation, e.g., an impaired ability to interact socially and immune suppression are also found in social insects. We studied the consequences of social isolation on behaviour and brain gene expression in the antTemnothorax nylanderi. Following isolation, workers interacted moderately less with adult nestmates, increased the duration of brood contact, and reduced the time spent self‐grooming, an important sanitary behaviour. Our brain transcriptome analysis revealed that only a few behaviour‐related genes had altered their expression with isolation time. Rather, many genes linked to immune system functioning and stress response had been downregulated. This probably sensitizes isolated individuals to various stressors, in particular because isolated workers exhibit reduced sanitary behaviour. We provide evidence of the diverse consequences of social isolation in social insects, some of which resemble those found in social mammals, suggesting a general link between social well‐being, stress tolerance, and immune competence in social animals.
The medical pause: Importance, processes and training
Authors: Lee Joy Yeonjoo , Szulewski Adam , Young John Q. , Donkers Jeroen , Jarodzka Halszka , van Merriënboer Jeroen J. G.
Published: March 2021

Research has shown that taking ‘timeouts’ in medical practice improves performance and patient safety. However, the benefits of taking timeouts, or pausing, are not sufficiently acknowledged in workplaces and training programmes. To promote this acknowledgement, we suggest a systematic conceptualisation of the medical pause, focusing on its importance, processes and implementation in training programmes. By employing insights from educational and cognitive psychology, we first identified pausing as an important skill to interrupt negative momentum and bolster learning. Subsequently, we categorised constituent cognitive processes for pausing skills into two phases: the decision‐making phase (determining when and how to take pauses) and the executive phase (applying relaxation or reflection during pauses). We present a model that describes how relaxation and reflection during pauses can optimise cognitive load in performance. Several strategies to implement pause training in medical curricula are proposed: intertwining pause training with training of primary skills, providing second‐order scaffolding through shared control and employing auxiliary tools such as computer‐based simulations with a pause function.
The DNA transporter ComEC has metal‐dependent nuclease activity that is important for natural transformation
Authors: Silale Augustinas , Lea Susan M. , Berks Ben C.
Published: March 2021

In the process of natural transformation bacteria import extracellular DNA molecules for integration into their genome. One strand of the incoming DNA molecule is degraded, whereas the remaining strand is transported across the cytoplasmic membrane. The DNA transport channel is provided by the protein ComEC. Many ComEC proteins have an extracellular C‐terminal domain (CTD) with homology to the metallo‐β‐lactamase fold. Here we show that this CTD binds Mn2+ ions and exhibits Mn2+‐dependent phosphodiesterase and nuclease activities. Inactivation of the enzymatic activity of the CTD severely inhibits natural transformation in Bacillus subtilis. These data suggest that the ComEC CTD is a nuclease responsible for degrading the nontransforming DNA strand during natural transformation and that this process is important for efficient DNA import.
Evaluation of activity and toxicity of combining clioquinol with ciclopirox and terbinafine in alternative models of dermatophytosis
Authors: da Costa Bárbara , Pippi Bruna , Berlitz Simone Jacobus , Carvalho Anderson Ramos , Teixeira Mario Lettieri , Külkamp‐Guerreiro Irene Clemes , Andrade Saulo F. , Fuentefria Alexandre Meneghello
Published: March 2021

Dermatophytosis is a superficial fungal infection that affects humans and is very common in small animals. The treatment using the most commonly used antifungals is failing, and new therapeutic alternatives are required to combat the resistance of these fungal infections. Previous studies by the group have shown that clioquinol is an important therapeutic alternative in the treatment of dermatophytosis. The object was to conduct studies of antidermatophytic activity and the irritant potential from the double and triple combinations of clioquinol, terbinafine and ciclopirox in ex vivo and in vivo alternative models. To evaluate the irritant potential of antifungal combinations, the alternative HET‐CAM method (chicken egg test chorioallantoic membrane) was used. Ex vivo models were used to assess the effectiveness of antifungal combinations, using pig hooves and veterinary fur. Any possible tissue damage was to assess through in histopathology of swine ears. HET‐CAM results showed that all combinations can be classified as non‐irritating, corroborated by the results of the histopathological evaluation of the pig's ear skin. Only the double combinations managed to remove 100% of the colony‐forming units (CFU) formed on the pig's hooves. The clioquinol + terbinafine combination and the triple combination were more effective than clioquinol + ciclopirox in eradicating the preformed biofilm in fur of veterinary origin. These results show the potential of formulations of clioquinol in combination with antifungals for use in humans and in the veterinary field to combat dermatophytosis, as an important alternative therapy, for use in the near future.
Analysis of contractile segment impedance during straight leg raise maneuver using high‐resolution impedance manometry increases diagnostic yield in reflux disease
Authors: Wong Ming‐Wun , Liu Tso‐Tsai , Yi Chih‐Hsun , Lei Wei‐Yi , Hung Jui‐Sheng , Omari Taher , Cock Charles , Liang Shu‐Wei , Gyawali Chandra Prakash , Chen Chien‐Lin
Published: March 2021

Background

Contractile segment impedance (CSI) obtained from high‐resolution impedance manometry (HRIM) is a measure of mucosal integrity that predicts gastroesophageal reflux disease (GERD). While straight leg raise (SLR) maneuver augments esophageal peristaltic vigor, it remains unclear whether SLR affects CSI values. This study was aimed to evaluate whether CSI with SLR is feasible and useful to complement the diagnosis of GERD.

Methods

We prospectively recruited 48 patients with typical GERD symptoms who underwent esophagogastroduodenoscopy, HRIM with SLR maneuver, and multichannel intraluminal impedance‐pH (MII‐pH) testing. The capability of mean nocturnal baseline impedance (MNBI), resting baseline impedance (RBI), CSI with or without SLR maneuver in predicting GERD was assessed using receiver operating characteristics (ROC) analysis.

Key Results

Among 20 GERD patients and 28 non‐GERD patients, all values of impedance‐based metrics were lower in GERD patients compared to non‐GERD patients (p < 0.001). For GERD identification, area under receiver operating characteristic curve (AUROC) values of CSI with SLR maneuver, CSI, MNBI, and RBI were 0.901, 0.858, 0.865, and 0.797. Particularly in ineffective esophageal motility (IEM) patients, SLR maneuver increased mean distal contractile integral from 436 to 828.7 mmHg.s.cm (p = 0.018) and enhanced AUROC values of CSI for GERD identification from 0.917 to 0.958.

Conclusions & Inferences

CSI measurement during HRIM appears to be a reliable, time‐saving, and less invasive tool for complementing GERD diagnosis. Our results also suggest a simple SLR maneuver during HRIM could enhance diagnostic accuracy of CSI for GERD identification especially in IEM patients.
Anorectal manometry to diagnose dyssynergic defecation: Systematic review and meta‐analysis of diagnostic test accuracy
Authors: Ortengren Alexandra R. , Ramkissoon Resham A. , Chey William D. , Baker Jason R. , Staller Kyle , Iturrino Johanna , Shah Eric D.
Published: March 2021

Background

Chronic constipation is a common condition, and dyssynergic defecation underlies up to 40% of cases. Anorectal manometry is recommended to assess for dyssynergic defecation among chronically constipated patients but remains poorly standardized. We aimed to evaluate the diagnostic accuracy of anorectal manometry and determine optimal testing parameters.

Methods

We performed a systematic review with meta‐analysis of diagnostic test accuracy including cohort studies of chronically constipated patients and case–control studies of patients with dyssynergic defecation or healthy controls. Meta‐analysis was performed to determine summary sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CI).

Key Results

A total of 15 studies comprising 2140 patients were included. Including all studies (estimating optimal diagnostic accuracy), the AUC was 0.78 [95% CI 0.72–0.82], summary sensitivity was 79% [61%–90%], and summary specificity was 64% [44%–79%] to diagnose dyssynergic defecation. In cohort studies only (estimating real‐world diagnostic accuracy), the AUC was 0.72 [0.66–0.77], summary sensitivity was 86% [64%–95%], and summary specificity was 49% [30%–68%]. Employing three consecutive simulated defecation attempts improved sensitivity to 94%. A fourth simulated defecation maneuver with air insufflation may improve accuracy. Measuring anorectal pressures to identify complex dyssynergic patterns did not improve real‐world diagnostic accuracy estimates over anal pressure measurement alone. Choice of manometry system did not impact diagnostic accuracy.

Conclusions & Inferences

Following the current iteration of the London consensus protocol (three simulated defecation attempts measuring anal relaxation), the role of anorectal manometry in evaluating dyssynergic defecation appears limited. Future iterations of this protocol may improve diagnostic accuracy.
Reference high‐resolution manometry values after magnetic sphincter augmentation
Authors: Siboni Stefano , Ferrari Davide , Riva Carlo Galdino , Sozzi Marco , Lazzari Veronica , Milani Valentina , Bonavina Luigi
Published: March 2021

Background

Magnetic sphincter augmentation (MSA) is an innovative antireflux procedure that can improve lower esophageal sphincter (LES) competency and reduce symptoms of gastroesophageal reflux disease (GERD). Some patients report postoperative dysphagia. To date, no studies have described reference high‐resolution manometry (HRM) values after MSA implantation.

Methods

High‐resolution manometry was performed in patients free of dysphagia after MSA with or without concurrent crura repair. Reference values for all parameters of the Chicago Classification were defined as those between the 5th and 95th percentiles. The contribution of concurrent crura repair to LES competency and to reference values was also analyzed.

Key Results

Eighty‐four patients met the study inclusion criteria. The upper limit of normality for integrated relaxation pressure (IRP) and intrabolus pressure (IBP) was 20.2 mmHg and 30.3 mmHg, respectively. Both variables were higher after MSA compared to normative Chicago Classification v3.0 values. The Distal Contractile Integral upper limit was in the range of normality. Patients undergoing crura repair had a significantly higher IRP (p = 0.0378) and lower GERDQ‐A scores (p = 0.0374) and Reflux Symptom Index (p = 0.0030) compared to those who underwent MSA device implantation alone.

Conclusion & Inferences

This study provides HRM reference values for patients undergoing successful MSA implantation. Crural repair appears to be a key component of LES augmentation and is associated with improved clinical outcomes.
Mary Shepherd on the role of proofs in our knowledge of first principles
Authors: Folescu M.
Published: March 2021

This paper examines the role of reason in Shepherd's account of acquiring knowledge of the external world via first principles. Reason is important, but does not have afoundationalrole. Certain principles enable us to draw the required inferences for acquiring knowledge of the external world. These principles are basic, foundational and, more importantly, self‐evident and thus justified in other ways than by demonstration. Justificatory demonstrations of these principles are neither required, nor possible. By drawing on textual and contextual evidence, I will show that Shepherd should have said that we know the first principles of any science, in general, and that “everything which begins to exist must have a cause”, in particular, via intuition, not via reason. Reasoning about such principles can help their self‐evidence shine through in certain cases; their justification, and our being justified in believing them, does not come from this reasoning, however.
Chromosome number is key to longevity of polyploid lineages
Authors: Bowers John E. , Paterson Andrew H.
Published: March 2021

Polyploidy is ubiquitous and often recursive in plant lineages, most frequently resulting in extinction but occasionally associated with great evolutionary success. However, instead of chromosome numbers exponentially increasing due to recurrent polyploidy, most angiosperm species have fewer than 14 chromosome pairs. Following genome duplication, diploidisation can render one copy of essential genes nonfunctional without fitness cost. In isolated subpopulations, alternate (homoeologous) gene copies can be lost, creating incompatibilities that reduce fitness of hybrids between subpopulations, constraining exchange of favourable genetic changes and reducing species fitness. When multiple sets of incompatible genes are genetically linked, their deleterious effects are not independent. The effective number of independently acting sets of incompatible loci in hybrids is limited by chromosome number and recombination. Therefore, species with many chromosomes are subject to a higher fitness penalty during diploidisation. Karyotypic changes, especially fusions, that reduce gene flow are normally fitness disadvantages, but during the diploidisation process, can increase fitness by reducing mixing of differentially diploidised alleles. Fitness penalties caused by diploidisation favour accelerated karyotypic change, with each change increasing barriers to gene flow, contributing to speciation. Lower chromosome numbers and increased chromosome fusions confer advantages to surviving the diploidisation process following polyploid formation, by independent mechanisms.
Feasibility and repeatability of ocular biometry measured with Lenstar LS 900 in a large group of children and adolescents
Authors: Rauscher Franziska G , Hiemisch Andreas , Kiess Wieland , Michael Ralph
Published: March 2021

Purpose

To evaluate the feasibility and repeatability of Lenstar LS 900 biometry measurements in a paediatric population.

Methods

Children were examined as part of the LIFE Child Study (Leipzig Research Centre for Civilization Diseases), a population‐based study in Leipzig, Germany. Altogether, 1917 children, aged from 3.5 to 17.5 years, were assessed with the Haag Streit Lenstar LS 900. Three consecutive measurements of the right eye were analysed for axial length, central corneal thickness, anterior chamber depth, aqueous depth, lens thickness and flat and steep corneal radii. The number of successful measurements and repeatability were evaluated for each parameter and three age bands (3.5 to 6.5 years, 6.5 to 10.5 years and 10.5 to 17.5 years).

Results

Best measurement feasibility was found for axial length and central corneal thickness (91% to 100%), followed by flat and steep corneal radii (86% to 100%), anterior chamber and aqueous depth (76% to 92%) and lens thickness (50% to 81%), with higher numbers for older children. Repeatability values (in mm) were: axial length 0.025 to 0.035; central corneal thickness 0.003 to 0.027; aqueous depth 0.024 to 0.058; anterior chamber 0.024 to 0.054; lens thickness 0.034 to 0.067. An overall trend showed better repeatability for older children, especially for central corneal thickness, aqueous depth and lens thickness.

Conclusions

For ocular biometry in the paediatric population, axial length, central corneal thickness, flat and steep corneal radii can be measured very reliably even in children from 4 years old onward using the Lenstar LS 900. Lens thickness can be quantified in a limited number of younger children. Repeatability was high for all variables investigated. Repeatability improved with age, reaching adult values in the adolescent age band. Established repeatability limits can be applied in future studies as a quality parameter.
Crystalline lens transmittance spectra and pupil sizes as factors affecting light‐induced melatonin suppression in children and adults
Authors: Eto Taisuke , Ohashi Michihiro , Nagata Kotaro , Shin Nakyeong , Motomura Yuki , Higuchi Shigekazu
Published: March 2021

Purpose

To investigate the contributions of ocular crystalline lens transmittance spectra and pupil size on age‐related differences in the magnitude of light‐induced melatonin suppression at night. The first aim was to demonstrate that spectral lens transmittance in children can be measured in vivo with a Purkinje image‐based system. The second aim was to test the hypothesis that the magnitude of melatonin suppression in children is enhanced by larger pupils and higher lens transmittance of short wavelengths.

Methods

Fourteen healthy children and 14 healthy adults participated in this study. The experiment was conducted for two nights in our laboratory. On the first night, the participants spent time under dim light conditions (<10 lux) until one hour after their habitual bedtime (BT+1.0). On the second night, the participants spent time under dim light conditions until 30 min before their habitual bedtime (BT‐0.5). They were then exposed to LED light for 90 min up to BT+1.0. Individual pupil sizes were measured between BT and BT+1.0 for both conditions. Lens transmittance spectra were measured in vivo using the Purkinje image‐based system during the daytime. Non‐visual photoreception was calculated from lens transmittance and pupil size. This was taken as an index of the influence of age‐related ocular changes on the non‐visual photopigment melanopsin.

Results

Measured lens transmittance in children was found to be higher than for adults, especially in the short wavelength region (p < 0.001). Pupil size in children was significantly larger than that of adults under both dim (p = 0.003) and light (p < 0.001) conditions. Children’s non‐visual photoreception was 1.48 times greater than that of adults, which was very similar to the finding that melatonin suppression was 1.52 times greater in children (n = 9) than adults (n = 9).

Conclusions

Our Purkinje image‐based system can measure children’s lens transmittance spectra in vivo. Lens transmittance and pupil size may contribute to differences in melatonin suppression between primary school children and middle‐aged adults.
CRISPR/Cas9‐based discovery of maize transcription factors regulating male sterility and their functional conservation in plants
Authors: Jiang Yilin , An Xueli , Li Ziwen , Yan Tingwei , Zhu Taotao , Xie Ke , Liu Shuangshuang , Hou Quancan , Zhao Lina , Wu Suowei , Liu Xinze , Zhang Shaowei , He Wei , Li Fan , Li Jinping , Wan Xiangyuan
Published: March 2021

Identifying genic male‐sterility (GMS) genes and elucidating their roles are important to unveil plant male reproduction and promote their application in crop breeding. However, compared with Arabidopsis and rice, relatively fewer maize GMS genes have been discovered and little is known about their regulatory pathways underlying anther and pollen development. Here, by sequencing and analysing anther transcriptomes at 11 developmental stages in maize B73, Zheng58 and M6007 inbred lines, 1100 transcription factor (TF) genes were identified to be stably differentially expressed among different developmental stages. Among them, 14 maize TF genes (9 types belonging to five TF families) were selected and performed CRISPR/Cas9‐mediated gene mutagenesis, and then, 12 genes in eight types, including ZmbHLH51, ZmbHLH122, ZmTGA9‐1/‐2/‐3, ZmTGA10, ZmMYB84, ZmMYB33‐1/‐2, ZmPHD11 and ZmLBD10/27, were identified as maize new GMS genes by using DNA sequencing, phenotypic and cytological analyses. Notably, ZmTGA9‐1/‐2/‐3 triple‐gene mutants and ZmMYB33‐1/‐2 double‐gene mutants displayed complete male sterility, but their double‐ or single‐gene mutants showed male fertility. Similarly, ZmLBD10/27 double‐gene mutant displayed partial male sterility with 32.18% of aborted pollen grains. In addition, ZmbHLH51 was transcriptionally activated by ZmbHLH122 and their proteins were physically interacted. Molecular markers co‐segregating with these GMS mutations were developed to facilitate their application in maize breeding. Finally, all 14‐type maize GMS TF genes identified here and reported previously were compared on functional conservation and diversification among maize, rice and Arabidopsis. These findings enrich GMS gene and mutant resources for deeply understanding the regulatory network underlying male fertility and for creating male‐sterility lines in maize.
De novo collapsing glomerulopathy in a pediatric kidney transplant recipient with COVID‐19 infection
Authors: Levenson Emma , Shepherd Tara N. , Aviles Diego , Craver Randall , Ehlayel Abdulla , Love Gordon L. , Simms K'Joy , Straatmann Caroline , Ashoor Isa F.
Published: March 2021

The negative impact of COVID‐19 on adults with underlying chronic kidney disease, including kidney transplant recipients, has been well documented. Children have a less severe presentation and better prognosis compared to adults. However, little is known regarding the spectrum of COVID‐19 infection in children and adolescents with underlying autoimmune disorders necessitating solid organ transplant and long‐term immunosuppressive therapy. Case Report. An adolescent male developed end‐stage kidney disease secondary to microscopic polyangiitis requiring a living‐donor kidney transplant. Six years later, he developed antibody‐mediated rejection of his kidney transplant. During his rejection treatment course, he contracted SARS‐CoV‐2 and developed new‐onset nephrotic syndrome with severe acute kidney injury. Kidney transplant biopsy revealed de novo collapsing focal segmental glomerulosclerosis on a background of chronic active antibody mediated rejection. Immunostaining for SARS‐CoV‐2 on the biopsy specimen demonstrated positive staining of the proximal tubular epithelium consistent with intra‐renal viral infection. Pulse corticosteroids, intravenous immunoglobulin, and temporary reduction of anti‐metabolite therapy resulted in successful recovery with return of graft function back to pre‐infection baseline. This case highlights the clinical conundrum of treating kidney transplant recipients with active rejection in the midst of the COVID‐19 pandemic. Pediatric kidney transplant recipients can develop severe COVID‐19‐related kidney complications. Judicious immunosuppression modulation is necessary to balance infection and rejection risk.
Kidney transplantation in children in KwaZulu‐Natal, South Africa
Authors: Sinada Nisreen Seed Ahmed , Naicker Elaene , Tinarwo Partson , Bhimma Rajendra
Published: March 2021

Background

CKF is an overwhelming illness, especially in children. Kidney transplantation is considered the definitive management of CKF. It has substantial benefits, including increased patient survival, improved skeletal growth, social adjustment, neuropsychological development, and better quality of life compared to chronic dialysis.

Methods

This is a retrospective, clinical, observational study in 13 children ≤16 years old who underwent kidney transplantation at IALCH in KwaZulu‐Natal, South Africa, from May 2015 to December 2019.

Results

Over 4 years and 7 months, 13 kidney transplants were performed; 7 (53.8%) were males, and 6 (46.2%) were females. Eleven (84.6%) were Black African and 2 (15.4%) Indian children. The mean age ± (SD) of transplantation was 10.1 ± 2.8 years (range 5.8–15.8). Eight (61.5%) children were from a rural setting. The mean ± (SD) duration of follow‐up was 29.5 ± 15.9 months. All kidney transplants done were from live related donors; 8 (61.5%) were parents of the recipients. None were pre‐emptive transplants. Graft loss occurred in 2 (15.4%) children with 100% patient survival. Two (15.4%) children developed acute rejection.

Conclusions

The commissioning of transplant services in KwaZulu‐Natal, South Africa, has improved access to this modality of treatment, particularly in our Black African patients. The significant limitations we experienced were a shortage of cadaveric donors and resource limitations with no dedicated transplant unit for pediatric patients together with staffing constraints. Enhancing patient and healthcare personal education will hopefully overcome cultural and religious barriers to organ donation.
Perioperative fatal pulmonary embolism in a pediatric liver transplant recipient
Authors: Jamil Omar , Fung John , Kelly Dympna , Azzam Ruba
Published: March 2021

Patients with cirrhotic liver disease are in a state of fluctuating hemostatic balance. Hepatic synthetic dysfunction is commonly complicated by coagulation disorders that constitute an important parameter of most prognostic scores. The dominant feature of this dysfunction is bleeding tendencies, but cirrhotic patients may also exhibit inappropriate clotting and pro‐coagulation placing them at risk for thromboembolism. We present a case of perioperative fatal pulmonary embolism in an 8‐year‐old patient with biliary cirrhosis secondary to drug‐induced vanishing bile duct syndrome undergoing a deceased donor liver transplant. The massive pulmonary embolism occurred intra‐operatively after reperfusion of the donor liver. Despite the initiation of extracorporeal membrane oxygenation, the postoperative course was complicated by bleeding and the patient expired. This unique case highlights the need for venous thromboembolism prevention by screening and prophylaxis prior to liver transplant in at least a subpopulation of pediatric patients. While the risk of thrombosis postoperatively in pediatrics patients is well known, the preoperative risk is less frequently described and deserves attention and practice changing action.