bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorectal patients’ readiness for hospital discharge following management of enhanced recovery after surgery pathway
Authors: Yang Jie , He Yuhua , Jiang Lili , Li Ka
Published: February 2020

The aim of this study was to ascertain the status quo of perceived readiness for hospital discharge in colorectal cancer patients who underwent enhanced recovery pathway and identify the variables that affect patients’ perceptions about their readiness for discharge.

A cross-sectional survey was conducted in West China Hospital, Sichuan University. The Readiness for Hospital Discharge Scale and the Quality of Discharge Teaching Scale were delivered to 130 colorectal cancer (CRC) patients who underwent enhanced recovery pathway. Data collection was carried out 4 hours before discharge.

The total score of readiness for hospital discharge was 149.86 ± 33.65. The multiple linear regression analysis revealed that the quality of discharge teaching, discharge to a rehabilitative institution were associated with the readiness for hospital discharge.

The level of CRC patients’ readiness for hospital discharge needs to be improved. Medical staff should improve the quality of discharge guidance and pay more attention to patients transferred to rehabilitation institutions when they leave hospital.
Effects of vitamin C supplementation on essential hypertension
Authors: Guan Yuanyuan , Dai Pengju , Wang Hongwu
Published: February 2020

Background:

Vitamin C as a supplement to treat hypertension has been proposed. However, it remains controversial whether vitamin C can improve blood pressure in patients with primary hypertension.

Objectives:

To analyze the effect of vitamin C (VitC) supplementation on systolic (SBP) and diastolic (DBP) blood pressure in patients with essential hypertension.

Methods:

We searched the Chinese Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, WANFANG Data, Cochrane Library, National Library of Medicine's PubMed, EMBASE, and other databases until June 2019. Eight RCTs involving 614 participants were analyzed. SBP and DBP before and after VitC supplementation were compared between the intervention and control groups. The risk of bias of individual studies was assessed using the Cochrane Collaboration risk of bias tool. Two reviewers selected studies independently of each other. The Cochrane Collaboration Review Manager 5.3 was used to perform the meta-analysis.

Results:

There was a significant difference in the change of SBP (weighted mean difference [WMD] = −4.09; 95% confidence interval [CI] −5.56, −2.62; P < .001) and DBP (WMD = −2.30; 95% CI −4.27, −.331; P = .02) between the groups. Further, there was a significant difference in the SBP (WMD = -3.75, 95% CI -6.24, -1.26, P = .003) and DBP (WMD = −3.29, 95% CI −5.98, −.60, P = .02) for the subgroup with an age ≥60 years and that with ≥35 participants. In the subgroup analysis, result for SBP with a study duration ≥6 weeks was statistically significant different (WMD = −4.77; 95% CI −6.46, −3.08; P < .001). For an intervention dose of VitC ≥500 mg daily, SBP was statistically significant (WMD = −5.01; 95% CI −8.55, −1.48; P = .005).

Conclusion:

VitC supplementation resulted in a significant reduction of blood pressure in patients with essential hypertension.
The disadvantage of morning blood pressure management in hypertensive patients
Authors: Liu Kai , Xu Ying , Gong Shenzhen , Li Jiangbo , Li Xinran , Ye Runyu , Liao Hang , Chen Xiaoping
Published: February 2020

To investigate whether the control of morning blood pressure (MBP) reflects the control of blood pressure (BP) in other periods (daytime, nighttime and 24-hour) and to assess whether morning BP displays a closer association with subclinical target organ damage (TOD) than the BP measured in other periods.

One thousand one hundred forty patients with primary hypertension who completed subclinical TOD detection and 24-hour ambulatory BP monitoring were included in the analysis. Pearson correlation analysis, Kappa consistency test, multiple linear regression analysis, and area under the receiver operating curve were used to analyze the data.

Morning BP and daytime BP displayed good agreement, but not 24-hour BP , particularly the nighttime BP (all P < .001). Approximately 39.4% of the hypertensive patients receiving drug treatment who had achieved control of the morning BP presented masked nocturnal hypertension, which was associated with worse subclinical TOD. The BP measured in all periods correlated with subclinical TOD, and the correlation was more obvious in the treatment subgroup. However, morning BP did not independently affect subclinical TOD. Morning BP appeared to exhibit less discriminatory power than nighttime BP, particularly with respect to the urinary albumin to creatinine ratio.

The use of morning BP for monitoring during hypertension management may not be enough. Masked uncontrolled nocturnal hypertension should be screened when morning BP is controlled.
Efficacy and safety of cefoperazone-sulbactam in empiric therapy for febrile neutropenia
Authors: Lan Shao-Huan , Chang Shen-Peng , Lai Chih-Cheng , Lu Li-Chin , Tang Hung-Jen
Published: February 2020

Purpose:

This meta-analysis assessed the clinical efficacy and safety of cefoperazone-sulbactam for empiric therapy febrile neutropenia.

Methods:

The PubMed, Web of Science, EBSCO, Cochrane Library, Ovid Medline, EMBASE, and ClinicalTrial.gov database were searched through May 10, 2019. Only clinical trials comparing cefoperazone-sulbactam with other antibiotics for empiric treatment of febrile neutropenia were included. The primary outcome was treatment success without modification, and the secondary outcomes were all-cause mortality and adverse events (AEs).

Results:

Ten randomized controlled trials (RCTs) and 1 retrospective cohort study were included. Overall, cefoperazone-sulbactam exhibited a treatment success rate similar to those of comparator drugs for the treatment of febrile neutropenia (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.85 to 1.24, I
2 = 0%). A similar finding was noted in pooled analysis of 10 RCTs (OR, 1.07; 95% CI, 0.88 to 1.30, I
2 = 0%). Subgroup analysis showed that cefoperazone-sulbactam had a treatment success rate similar to the rates of comparators for adults (OR, 1.10; 95% CI, 0.88 to 1.38, I
2 = 0%) and children (OR, 0.96; 95% CI, 0.63 to 1.46, I
2 = 0%). Cefoperazone-sulbactam did not differ significantly from comparators in the risks of all-cause mortality (OR, 0.96; 95% CI, 0.58 to 1.58, I
2 = 0%) or common AEs, namely rash, nausea/vomiting, and superinfection.

Conclusion:

The clinical efficacy and tolerability of cefoperazone-sulbactam are comparable to those of comparator drugs in the treatment of febrile neutropenia.
The Management of Young Children With a Likely Infectious Condition Presenting Moderate to Severe Neutropenia
Authors: Larouche Valérie , Pelland-Marcotte Marie-Claude , Blanchet Marie-Ève , Simonyan David , Bélanger Richard E.
Published: February 2020

Objective:

The objective of this study was to describe the outcome of healthy children presenting with newly-diagnosed neutropenia in an infectious context.

Results:

A total of 184 episodes of neutropenia were included in children 3 months to 5 years of age. There were 118 (64%) episodes of moderate neutropenia and 66 (36%) of severe neutropenia (SN). SN episodes were more likely related to intensification of antibiotic regimen used and further investigations. The median duration of neutropenia was 8.5 days. Chronic benign neutropenia occurred in 7 (4%) patients.

Conclusion:

SN led to intensification of antibiotic therapy, but no children encountered an unfavorable outcome and the neutropenia episodes were short-lived.
Carpal Tunnel Syndrome and Meralgia Paresthetica in Pregnancy
Authors: Gooding Megan S. , Evangelista Victor , Pereira Leonardo
Published: February 2020

Importance

Carpal tunnel syndrome and meralgia paresthetica are 2 common neuropathies complicating pregnancy. Each of these causes significant discomfort but can be diagnosed and treated safely during pregnancy.

Objective

This article outlines the existing literature diagnosis, treatment, and prognosis of carpal tunnel syndrome and meralgia paresthetica, specifically looking at the implications during pregnancy. The aim is to provide a reference for physicians diagnosing and treating neuropathies in pregnant patients.

Evidence Acquisition

Existing literature on neuropathies during pregnancy, clinical presentation, and treatment options for both carpal tunnel syndrome and meralgia paresthetica was reviewed through a MEDLINE and PubMed search. Referenced articles were reviewed and used as primary source materials as appropriate.

Results

Carpal tunnel syndrome affects individuals of all ages and sexes but is more prevalent in women, particularly during pregnancy. Meralgia paresthetica can occur in various circumstances but is most commonly associated with prolonged second stage in lithotomy position. Multiple clinical signs and neurologic tests are useful to establish the diagnosis of either neuropathy. Effective treatment for carpal tunnel syndrome includes wrist splints, steroid and lidocaine injections, and release surgery. Optimal treatment of meralgia paresthetica remains controversial but includes nerve block injections and active release techniques.

Conclusions and Relevance

Neuropathies are common in pregnancy and can result in significant impairment. Accurate diagnosis is possible during pregnancy and can usually be accomplished with bedside neurologic tests. Treatment options can be safely considered during pregnancy and can result in symptomatic improvement and reduction in chronic symptoms.

Target Audience

Obstetricians and gynecologists, family physician

Learning Objectives

After completing this activity, the learner should be better able to describe the clinical features and diagnosis of carpal tunnel syndrome; explain treatment options for carpal tunnel syndrome in pregnancy; and identify risk factors and how to diagnose meralgia paresthetica.
Safety and Clinical Outcomes of Hospital in the Home
Authors: Sriskandarajah Shanthy , Ritchie Brett , Eaton Vaughn , Sluggett Janet K. , Hobbs Jodie G. , Daniel Santhosh , Reynolds Karen J.
Published: February 2020

Objectives

The aim of the study was to evaluate clinical outcomes and adverse events (AEs) experienced by patients treated within the Hospital in the Home (HITH) service of a major metropolitan hospital in South Australia.

Methods

A retrospective case note audit of 100 HITH episodes among adults who received continuous intravenous antimicrobial therapy via an elastomeric or electronic infusion device was undertaken. Age- and sex-adjusted binomial logistic regression analyses were undertaken to identify factors associated with major and minor AEs.

Results

Of the 100 patients included, 71 were male and the mean (SD) patient age was 62.8 (17.19) years. Elastomeric infusion devices were used for 98 patients. The mean (SD) HITH treatment duration was 20.1 (11.9) days. Overall, 130 AEs were documented for 72 patients (72%), of whom 12 patients experienced a major AE and 68 patients experienced a minor AE. There were 45 occasions among 23 patients where an infusion administered through an elastomeric device did not run to completion. Fifteen patients were readmitted to hospital. Minor AEs were more likely among people with more vascular line days (adjusted odds ratio [aOR] = 1.05; 95% confidence interval (CI) = 1.01–1.10 per day increase) and females (aOR = 4.43; 95% CI = 1.14–17.17). An increased number of vascular line days was associated with an increased likelihood of an incomplete infusion (aOR = 1.05; 95% CI = 1.01–1.09). Hospital readmission was more likely with increasing age (aOR = 1.06; 95% CI = 1.01–1.11 per year increase).

Conclusions

Adverse events need to be monitored carefully when HITH treatment is provided for extended periods.
Toward Universal HIV Treatment in Haiti: Time Trends in ART Retention After Expanded ART Eligibility in a National Cohort From 2011 to 2017
Authors: Puttkammer Nancy , Parrish Canada , Desir Yrvel , Hyppolite Nathaelf , Wagenaar Bradley H. , Joseph Nadjy , Hall Lara , Honoré Jean Guy , Robin Ermane , Perrin Georges , François Kesner
Published: February 2020

Background:

The World Health Organization (WHO) recommends universal antiretroviral therapy (ART) for persons living with HIV (PLWH), but evidence about effects of expanded ART access on ART retention in low-resource settings is limited.

Setting:

Haiti's Ministry of Health endorsed universal ART for pregnant women in March 2013 (Option B+) and for all PLWH in July 2016. This study included 51,579 ART patients from 2011 to 2017 at 94 hospitals and clinics in Haiti.

Methods:

This observational, retrospective cohort study described time trends in 6-month ART retention using secondary data, and compared results during 3 periods using an interrupted time series model: pre-Option B+ (period 1: 1/11–2/13), Option B+ (period 2: 3/13–6/16), and Test and Start (T&S, period 3: 7/16–9/17).

Results:

From the pre-Option B+ to the T&S period, the monthly count of new ART patients increased from 366/month to 877/month, and the proportion with same-day ART increased from 6.3% to 42.1% (P < 0.001). The proportion retained on ART after 6 months declined from 78.4% to 75.0% (P < 0.001). In the interrupted time series model, ART retention improved by a rate of 1.4% per quarter during the T&S period after adjusting for patient characteristics (adjusted incidence rate ratio = 1.014; 95% confidence interval: 1.002 to 1.026, P < 0.001). However, patients with same-day ART were 14% less likely to be retained compared to those starting ART >30 days after HIV diagnosis (adjusted incidence rate ratio = 0.86; 95% confidence interval: 0.84–0.89, P < 0.001).

Conclusions:

Achieving targets for HIV epidemic control will require increasing ART retention and reducing the disparity in retention for those with same-day ART.
Myositis-Specific Antibodies and Myositis-Associated Antibodies in Patients With Idiopathic Inflammatory Myopathies From the PANLAR Myositis Study Group
Authors: González-Bello Yelitza , Garcia-Valladares Ignacio , Reyes-Pérez Itzel Viridiana , García-Cerda Daniel , Medrano-Ramírez Gabriel , Navarro-Zarza José E. , Andrade-Ortega Lilia , Maradiaga-Ceceña Marco , Cardenas-Anaya Alicia , Nava-Zavala Arnulfo H. , Orozco-Barocio Gerardo , Vázquez-Del Mercado Mónica , Rojo-Mejia Armando , Loyo Esthela , Gottschalk Paola , Iglesias-Gamarra Antonio , Vega Kelly , Rojas Cilia , Mantilla Rubén , Gómez Graciela , García-Kutzbach Abraham , Fritzler Marvin J. , García-De La Torre Ignacio
Published: February 2020

Background

Dermatomyositis (DM) and polymyositis (PM) are forms of idiopathic inflammatory myopathies (IIMs), which are associated with the production of autoantibodies that are useful in the diagnosis and prognosis of the disease.

Objective

The aim of this study was to determine the frequency of antinuclear autoantibodies (ANAs), myositis-specific autoantibodies (MSAs), and myositis-associated autoantibodies (MAAs) in 6 Latin American countries.

Methods

Two hundred ten patients with IIM were included in this cross-sectional study from 2014 to 2017: 112 from Mexico, 46 from Colombia, 20 from Peru, 16 from the Dominican Republic, 10 from Argentina, and 6 from Guatemala. Antinuclear autoantibodies were detected by indirect immunofluorescence on HEp-2 cells. MSAs and MAAs were tested by a line immunoassay method. Mann-Whitney U and χ2 tests were used for statistical analysis.

Results

Of the 210 IIM patients, 139 (66.2%) had DM, 59 (28%) PM, and 12 (5.7%) juvenile DM. The mean age was 43.5 (6–79 years); 158 (75.2%) were female, and 52 (24.8%) were male. The overall frequency of ANA was 60%. The most frequent patterns were fine speckled (AC-4) (78.3%) and cytoplasmic (AC-19) (6.45%). The most frequent MSA were anti–Mi-2 (38.5%) and anti–Jo-1 (11.9%). Anti–Mi-2 was more frequent in patients from Colombia (40.1%). The MAA more frequent were anti–Ro-52/TRIM21 (17.6%) and anti–PM-Scl75 (7.5%).

Conclusions

This is the first study of ANA, MSA, and MAA in patients from 6 countries from the Panamerican League against Rheumatism myositis study group. We observed a general prevalence of 60% of ANA. In relation to MSA and MAA, anti–Mi-2 was the more frequent (38.5%).
Executive Summary of the American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults
Authors: Patel Kepal N. , Yip Linwah , Lubitz Carrie C. , Grubbs Elizabeth G. , Miller Barbra S. , Shen Wen , Angelos Peter , Chen Herbert , Doherty Gerard M. , Fahey Thomas J. , Kebebew Electron , Livolsi Virginia A. , Perrier Nancy D. , Sipos Jennifer A. , Sosa Julie A. , Steward David , Tufano Ralph P. , McHenry Christopher R. , Carty Sally E.
Published: February 2020

Objective:

The aim of this study was to develop evidence-based recommendations for safe, effective and appropriate thyroidectomy.

Background:

Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the United States.

Methods:

The medical literature from January 1, 1985 to November 9, 2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content.

Results:

These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches Laryngology Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation.

Conclusion:

Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.
Is the Resected Gastric Volume Effective in the Complication of Laparoscopic Sleeve Gastrectomy?
Authors: Seyit Hakan , Tulubas Evrim K.
Published: February 2020

Background:

To determine the relationship between the resected gastric volume (RGV) and the results of laparoscopic sleeve gastrectomy (LSG).

Methods:

The study included 333 patients with LSG. Patients were divided into 4 groups according to RGV: 600 to 999 cm3 as Group 1, 1000 to 1499 cm3 as Group 2, 1500 to 1999 cm3 as Group 3, and ≥2000 cm3 consists the Group 4. Prospectively collected data at first month, sixth month, and at first year were retrospectively reviewed. The percentage of the reduction in body mass index and the excess weight loss and remission of comorbid diseases were recorded.

Results:

Preoperative demographic data were similar within groups. No statistically significant difference was observed between the groups in terms of the changes in excess weight loss. The major complication rates were highest in Group 4 and the difference between the groups was statistically significant (P=0.012).

Conclusions:

The results of this study showed that different RGV do not affect the results of LSG, furthermore in patients with RGV ≥2000 cm3, surgeons should be careful for major complications.
The Association Between Macroscopic Arteriosclerosis of the Renal Artery, Microscopic Arteriosclerosis, Organ Discard, and Kidney Transplant Outcome
Authors: Keijbeck Anke , Veenstra Rob , Pol Robert A. , Konijn Cynthia , Jansen Nichon , van Goor Harry , Hoitsma Andries J. , Peutz-Kootstra Carine J. , Moers Cyril
Published: February 2020

Background.

During organ retrieval, surgeons estimate the degree of arteriosclerosis and this plays an important role in decisions on organ acceptance. Our study aimed to elucidate the association between macroscopic renal artery arteriosclerosis, donor kidney discard, and transplant outcome.

Methods.

We selected all transplanted and discarded kidneys in the Netherlands between January 1, 2000, and December 31, 2015, from deceased donors aged 50 y and older, for which data on renal artery arteriosclerosis were available (n = 2610). The association between arteriosclerosis and kidney discard, the relation between arteriosclerosis and outcome, and the correlation between macroscopic and microscopic arteriosclerosis were explored.

Results.

Macroscopic arteriosclerosis was independently associated with kidney discard (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.02-1.80; P = 0.03). Arteriosclerosis (any degree) was not significantly associated with delayed graft function (OR, 1.16; 95% CI, 0.94-1.43; P = 0.16), estimated glomerular filtration rate 1-y posttransplant (B, 0.58; 95% CI, –2.07 to 3.22; P = 0.67), and long-term graft survival (hazard ratio, 1.07; 95% CI, 0.86-1.33; P = 0.55). There was a significant association between mild arteriosclerosis and primary nonfunction (OR, 2.14; 95% CI, 1.19-3.84; P = 0.01). We found no correlation between macroscopic and histological arteriosclerosis, nor between histological arteriosclerosis and transplant outcome.

Conclusions.

Macroscopic arteriosclerosis of the renal artery was independently associated with kidney discard and somewhat associated with primary nonfunction posttransplant. However, there was no effect of arteriosclerosis on delayed graft function, estimated glomerular filtration rate at 1 y, or long-term graft survival. Our results are valid only after inevitable exclusion of discarded kidneys that had on average more arteriosclerosis. Hence, conclusions should be interpreted in the light of this potential bias.
Boosting Toll-like receptor 4 signaling enhances the therapeutic outcome of antibiotic therapy in pneumococcal pneumonia
Authors: Casilag Fiordiligie , Franck Sebastian , Matarazzo Laura , Figeac Martin , Michelet Robin , Kloft Charlotte , Carnoy Christophe , Sirard Jean-Claude
Published: February 2020

The emergence and spread of antibiotic resistance emphasize the need for alternative treatment strategies against bacterial infections. Boosting the host innate immunity is not only readily deployable in most individuals but can also mobilize many different antibacterial defenses. This study tested the hypothesis whereby stimulation of the innate immune receptor Toll-like receptor 4 (TLR4) can be combined with antibiotics in the treatment of invasive pneumonia. In a mouse model ofStreptococcus pneumoniaeinfection, a single oral administration of low-dose amoxicillin (AMX) or the systemic delivery of monophosphoryl lipid A (MPLA, a clinically-approved TLR4 activator) decreased the bacterial load in lung and spleen, although this was not sufficient for long-term survival. In contrast, a single treatment with a combination of MPLA and AMX induced significant bacterial clearance with little to no regrowth over time, and was associated with longer survival. Upregulation of genes related to granulocyte infiltration in lung tissue and elevation of blood levels of pro-inflammatory cytokines was immediate and transient in MPLA-treated mice; this indicates activation of the innate immune system in a context of infection. Combination treatment was associated with a well-preserved lung tissue architecture and more rapid recovery from inflammation - suggesting that immune activation by MPLA does not exacerbate pneumonia-induced damage. After AMX administration, plasma AMX concentrations rapidly reached the maximum and declined, whereas the downstream effects of MPLA extended beyond AMX elimination; these findings suggested a two-step effect. Our results demonstrated that leveraging host innate immunity increases the efficacy of antibiotic therapy in bacterial pneumonia.
Knowledge guided multi-level network inference
Authors: Ogris Christoph , Hu Yue , Arloth Janine , Müller Nikola S.
Published: February 2020

Constantly decreasing costs of high-throughput profiling on many molecular levels generate vast amounts of so-called multi-omics data. Studying one biomedical question on two or more omic levels provides deeper insights into underlying molecular processes or disease pathophysiology. For the majority of multi-omics data projects, the data analysis is performed level-wise, followed by a combined interpretation of results. Few exceptions exist, for example the pairwise integration for quantitative trait analysis. However, the full potential of integrated data analysis is not leveraged yet, presumably due to the complexity of the data and the lacking toolsets. Here we propose a versatile approach, to perform a multi-level integrated analysis: The Knowledge guIded Multi-Omics Network inference approach, KiMONo. KiMONo performs network inference using statistical modeling on top of a powerful knowledge-guided strategy exploiting prior information from biological sources. Within the resulting network, nodes represent features of all input types and edges refer to associations between them, e.g. underlying a disease. Our method infers the network by combining sparse grouped-LASSO regression with a genomic position-confined Biogrid protein-protein interaction prior. In a comprehensive evaluation, we demonstrate that our method is robust to noise and still performs on low-sample size data. Applied to the five-level data set of the publicly available Pan-cancer collection, KiMONO integrated mutation, epigenetics, transcriptomics, proteomics and clinical information, detecting cancer specific omic features. Moreover, we analysed a four-level data set from a major depressive disorder cohort, including genetic, epigenetic, transcriptional and clinical data. Here we demonstrated KiMONo’s analytical power to identify expression quantitative trait methylation sites and loci and show it’s advantage to state-of-the-art methods. Our results show the general applicability to the full spectrum multi-omics data and demonstrating that KiMONo is a powerful approach towards leveraging the full potential of data sets. The method is freely available as an R package (https://github.com/cellmapslab/kimono).
The role of CAPG in molecular communication between the embryo and the uterine endometrium: Is its function conserved in species with different implantation strategies?
Authors: Tinning Haidee , Taylor Alysha , Wang Dapeng , Constantinides Bede , Sutton Ruth , Oikonomou Georgios , Velazquez Miguel A. , Thompson Paul , Treumann Achim , O’Connell Mary J , Forde Niamh
Published: February 2020

During the pre-implantation period of pregnancy in eutherian mammals, changes to the uterine endometrium are required (both at the transcriptional and protein level) to facilitate the endometrium becoming receptive to an implanting embryo. We know that the developing conceptus (embryo and extraembryonic membranes) produces proteins during this developmental stage. We hypothesised that this common process in early pregnancy in eutheria may be facilitated by highly conserved conceptus-derived proteins such as macrophage capping protein CAPG. More specifically, we propose that CAPG may share functionality in modifying the transcriptome of the endometrial epithelial cells to facilitate receptivity to implantation in species with different implantation strategies, such as human and bovine. A recombinant bovine form of CAPG (91% sequence identity between bovine and human) was produced and bovine endometrial epithelial (bEECs) and stromal (bESCs) cells and human endometrial epithelial cells (hEECs) were cultured for 24 h with or without rbCAPG. RNA sequencing and quantitative real-time PCR analysis was used to assess the transcriptional response to rbCAPG (Control, vehicle, CAPG 10, 100, 1000 ng/ml: n=3 biological replicates per treatment per species). Treatment of bEECs with CAPG resulted in changes to 1052 transcripts (629 increased and 423 decreased) compared to vehicle controls, including those previously only identified as regulated by interferon-tau, the pregnancy recognition signal in cattle. Treatment of hEECs with bovine CAPG increased expression of transcripts previously known to interact with CAPG in different systems (CAPZB, CAPZA2, ADD1andADK) compared with vehicle controls (P<0.05). In conclusion, we have demonstrated that CAPG, a highly conserved protein in eutherian mammals elicits a transcriptional response in the endometrial epithelium in two species with different implantation strategies that may facilitate uterine receptivity.
Does methylation of NFATC1 and C-FOS genes are associated with post-menopausal osteoporosis?
Authors: Kalkan Rasime , Tosun Özgür
Published: February 2020

Genetic and epigenetic factors have an important role during the development of osteoporosis. RANK/RANKL pathway is important for the bone remodeling and NFATC1 and c-FOS are the downtargets of this pathway. Here, we report methylation status ofNFATC1andC-FOSgenes in post and premenopausal cases. In this study 30 pre-menopausal and 35 post-menopausal cases were included. MS-HRM was used for identification ofNFATC1andC-FOSmetyhylation.

NFATC1 were methylated in 11 of the 35 post-menopausal women and C-FOS were methylated in 6 of the postmenopausal women (p >0.005). Here, we found statistically significant association between unmethylation of NFATC1 and post-menopausal status. This result explains the epigenetic regulation of osteoclasts during the menopausal transition and our results can be used for epigenetic explanation of post-menopausal osteoporosis for the first time in the literature. Although the limited number of studies in this field makes our results crucial. Therefore, our results showed great value of epigenetic profile of post-menopausal women.
Bidirectional control of fear memories by the cerebellum through the ventrolateral periaqueductal grey
Authors: Frontera Jimena L. , Aissa Hind Baba , Sala Romain William , Mailhes-Hamon Caroline , Georgescu Ioana Antoaneta , Léna Clément , Popa Daniela
Published: February 2020

Fear conditioning is a form of associative learning that is known to involve brain areas, notably the amygdala, the prefrontal cortex and the periaqueductal grey (PAG). Here, we describe the functional role of pathways that link the cerebellum with the fear network. We found that the cerebellar fastigial nucleus (FN) sends glutamatergic projections to vlPAG that synapse onto glutamatergic and GABAergic vlPAG neurons. Chemogenetic and optogenetic manipulations revealed that the FN-vlPAG pathway controls bi-directionally the strength of the fear memory, indicating a role in the association of the conditioned and unconditioned stimuli, a function consistent with vlPAG encoding of fear prediction error. In addition, we found that a FN - thalamic parafascicular nucleus pathway, which may relay cerebellar influence to the amygdala, is involved in anxiety and fear expression but not in fear memory. Our results reveal the contributions to the emotional system of the cerebellum, which exerts a potent control on the strength of the fear memory through excitatory FN-vlPAG projections.
New pathogenic variants and insights into pathogenic mechanisms in GRK1-related Oguchi disease
Authors: Poulter James A. , Gravett Molly S. C. , Taylor Rachel L. , Fujinami Kaoru , De Zaeytijd Julie , Bellingham James , Rehman Atta Ur , Hayashi Takaaki , Kondo Mineo , Rehman Abdur , Ansar Muhammad , Donnelly Dan , Toomes Carmel , Ali Manir ,   UK Inherited Retinal Disease Consortium,   Genomics England Research Consortium, De Baere Elfride , Leroy Bart P. , Davies Nigel P. , Henderson Robert H. , Webster Andrew R. , Rivolta Carlo , Mahroo Omar A. , Arno Gavin , Black Graeme C. , McKibbin Martin , Harris Sarah A. , Khan Kamron N. , Inglehearn Chris F.
Published: February 2020

Purpose

Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB). The purpose of this study was to identify pathogenic GRK1 variants and use in-depth bioinformatic analyses to evaluate how their impact on protein structure could lead to pathogenicity.

Methods

Patients’ genomic DNA was sequenced by whole genome, whole exome or focused exome sequencing. Pathogenic variants, published and novel, were compared to nondisease associated missense variants. The impact ofGRK1missense variants at the protein level were then predicted using a series of computational tools.

Results

We identified eleven previously unpublished cases with biallelic pathogenic GRK1 variants, including seven novel variants, and reviewed allGRK1pathogenic variants. Further structure-based scoring revealed a hotspot for missense variants in the kinase domain. Additionally, to aid future clinical interpretation, we identified the bioinformatics tools best able to differentiate pathogenic from non-pathogenic variants.

Conclusion

We identified newGRK1pathogenic variants in Oguchi disease patients and investigated how disease-causing variants may impede protein function, giving new insights into the mechanisms of pathogenicity. All pathogenic GRK1 variants described to date have been collated into a Leiden Open Variation Database (http://dna2.leeds.ac.uk/GRK1_LOVD/genes/GRK1).
The helix bundle domain of primase RepB’ is required for dinucleotide formation and extension
Authors: Banchenko Sofia , Weise Chris , Lanka Erich , Saenger Wolfram , Geibel Sebastian
Published: February 2020

During DNA replication, primases synthesize oligonucleotide primers on single-stranded template DNA, which are then extended by DNA polymerases to synthesize a complementary DNA strand. Primase RepB’ of plasmid RSF1010 initiates DNA replication on two 40 nucleotide long inverted repeats, termed ssiA and ssiB, within the oriV of RSF1010. RepB’ consists of a catalytic domain and a helix bundle domain which are connected by long α-helix 6 and an unstructured linker. Previous work has demonstrated that RepB’ requires both domains for initiation of dsDNA synthesis in DNA replication assays. However, the precise functions of these two domains in primer synthesis have been unknown. Here we report that both domains of RepB’ are required to synthesizes a 10–12 nucleotide long DNA primer whereas the isolated domains are inactive. Mutational analysis of the catalytic domain indicates that the solvent-exposed W50 plays a critical role in resolving a hairpin structures formed by ssiA and ssiB. Three structurally conserved aspartates (D77, D78 and D134) of RepB’ catalyse the nucleotidyl transfer reaction. Mutations on the helix bundle domain are identified that either reduce the primer length to a dinucleotide (R285A) or abolish primer synthesis (D238A) indicating that the helix bundle domain is required to form and extend the initial dinucleotide synthesized by the catalytic domain.
Tudor staphylococcal nuclease acts as a docking platform for stress granule components inArabidopsis thaliana
Authors: Gutierrez-Beltran Emilio , Elander Pernilla H. , Dalman Kerstin , Crespo Jose Luis , Moschou Panagiotis N. , Uversky Vladimir N. , Bozhkov Peter V.
Published: February 2020

Adaptation to stress depends on the modulation of gene expression. Regulation of mRNA stability and degradation in stress granules (SGs), - cytoplasmic membraneless organelles composed of messenger ribonucleoprotein (mRNP) complexes, - plays an important role in fine-tuning of gene expression. In addition, SG formation can modulate stress signaling pathways by protein sequestration. Molecular composition, structure, and function of SGs in plants remain obscure. Recently, we established Tudor Staphylococcal Nuclease (TSN or Tudor-SN; also known as SND1) as integral component of SGs inArabidopsis thaliana. Here, we combined purification of TSN interactome with cell biology, reverse genetics and bioinformatics to study composition and function of SGs in plants. We found that under both normal (in the absence of stress) and stress conditions TSN interactome is enriched in the homologues of known mammalian and yeast SG proteins, in addition to novel or plant-specific SG components. We estimate that upon stress perception, approximately half of TSN interactors are recruited to SGsde novo, in a stress-dependent manner, while another half represent a dense protein-protein interaction network pre-formed before onset of stress. Almost all TSN-interacting proteins are moderately or highly disordered and approximately 20% of them are predisposed for liquid-liquid phase separation (LLPS). This suggests that plant SGs, similarly to mammalian and yeast counterparts, are multicomponent viscous liquid droplets. Finally, we have discovered that evolutionary conserved SNF1-related protein kinase 1 (SnRK1) interacts with TSN in heat-induced SGs and that SnRK1 activation critically depends on the presence of TSN and formation of SGs. Altogether, our results establish TSN as a docking platform for SG-associated proteins and important stress signal mediator in plants.
Commensal oralRothia mucilaginosaproduces enterobactin – a metal chelating siderophore
Authors: Uranga Carla , Arroyo Pablo , Duggan Brendan M. , Gerwick William H. , Edlund Anna
Published: February 2020

Next-generation sequencing studies of saliva and dental plaque from subjects in both healthy and diseased states have identified bacteria belonging to theRothiagenus as ubiquitous members of the oral microbiota. To gain a deeper understanding of molecular mechanisms underlying the chemical ecology of this unexplored group, we applied a genome mining approach that targets functionally important biosynthetic gene clusters (BGCs). All 45 genomes that were mined, representingRothia mucilaginosa, R. dentocariosaandR. aeria, harbored a catechol-siderophore-like BGC. To explore siderophore production further we grew the previously characterizedR. mucilaginosaATCC 25296 in liquid cultures, amended with glycerol, which led to the identification of the archetype siderophore enterobactin by using tandem Liquid Chromatography Mass Spectrometry (LC/MS/MS), High Performance Liquid Chromatography (HPLC), and Nuclear Magnetic Resonance (NMR) spectroscopy. Normally attributed to pathogenic gut bacteria,R. mucilaginosais the first commensal oral bacterium found to produce enterobactin. Co-cultivation studies includingR. mucilaginosaor purified enterobactin revealed that enterobactin reduced growth of certain strains of cariogenicStreptococcus mutansand pathogenic strains ofStaphylococcus aureus. Commensal oral bacteria were either unaffected by, reduced in growth, or induced to grow adjacent to enterobactin producingR. mucilaginosaor the pure compound. Taken together withRothia’s known capacity to ferment a variety of carbohydrates and amino acids, our findings of enterobactin production adds an additional level of explanation toR. mucilaginosa’s colonization success of the oral cavity. Enterobactin is the strongest Fe(III)-binding siderophore known, and its role in oral health requires further investigation.

Importance

The communication language of the human oral microbiota is vastly underexplored. However, a few studies have shown that specialized small molecules encoded by BGCs have critical roles such as in colonization resistance against pathogens and quorum sensing. Here, by using a genome mining approach in combination with compound screening of growth cultures, we identified that the commensal oral community membermucilaginosaharbors a catecholate-siderophore BGC, which is responsible for the biosynthesis of enterobactin. The iron-scavenging role of enterobactin is known to have positive effects on the host’s iron pool and negative effects on host immune function, however its role in oral health remains unexplored.R. mucilaginosawas previously identified as an abundant community member in cystic fibrosis, where bacterial iron cycling plays a major role in virulence development. With respect to iron’s broad biological importance, iron-chelating enterobactin may explainR. mucilaginosa’s colonization success in both health and disease.
Automated identification of multinucleated germ cells with U-Net
Authors: Bell Samuel , Zsom Andras , Conley Justin , Spade Daniel
Published: February 2020

Phthalic acid esters (phthalates) are male reproductive toxicants, which exert their most potent toxicity during a critical window of sensitivity in fetal development. In the fetal rat, exposure to phthalates reduces testosterone biosynthesis, alters the development of seminiferous cords and other male reproductive tissues, and induces the formation of abnormal multinucleated germ cells (MNGs). Identification of MNGs is a time-intensive process, and it requires specialized training to identify MNGs in histological sections. As a result, MNGs are not routinely quantified in phthalate toxicity experiments. In order to speed up and standardize this process, we have developed an improved method for automated detection of MNGs. Using hand-labeled histological section images with human-identified MNGs, we trained a convolutional neural network with a U-Net architecture to identify MNGs on unlabeled images. With unseen hand-labeled images not used in model training, we assessed the performance of the model, using five different configurations of the data. On average, the model reached near human accuracy, and in the best model, it exceeded it. The use of automated image analysis will allow data on this histopathological endpoint to be more readily collected for analysis of phthalate toxicity. Our trained model application code is available for download at github.com/brown-ccv/mngcount.
Tree bark scrape fungus: A potential source of laccase for application in bioremediation of non-textile dyes
Authors: Bhamare H.M. , Sayyed R. Z. , Marraiki Najat , Elgorban Abdallah M. , Syed Asad , El-Enshasy Hesham Ali
Published: February 2020

Although laccase has been recognized as a wonder molecule, and green enzyme, the use of low yielding fungal strains, poor production, purification, and low enzyme kinetics have hampered its larger-scale applications. Hence the present research was aimed to select high yielding fungal strains and to optimize the production, purification, and kinetics of laccase ofAspergillussp. HB_RZ4.Aspergillussp. HB_RZ4 produced a copious amount of laccase on under meso-acidophillic shaking conditions in a medium containing glucose and yeast extract. A 25 µM of CuSO4enhanced the enzyme yield. The enzyme was best purified on Sephadex G-100 column. Purified enzyme resembled with the laccase ofA. flavus. Kinetics of purified enzyme revealed the high substrate specificity and good velocity of reaction with ABTS as substrate. The enzyme was stable over a wide range of pH and temperature. The peptide structure of the purified enzyme resembled with the laccase ofA. kawachiiIFO 4308. The fungus decolorized various dyes independent of the requirement of a laccase mediator system (LMS).Aspergillussp. HB_RZ4 came out as a potent natural producer of laccase, it decolorized the dyes even in absence of LMS and thus can be used for bioremediation.
Allergen Extraction: Factors Influencing the Yield, Allergenicity and Sensitivity of Immunoassays
Authors: Soares João Ricardo Almeida , Guimarães Isabelle Mazza , de Souza Oliveira Ana Luísa , das Neves Faccini Claudia Regina Josetti , de Aquino Mattos Erika Bertozzi , Rodrigues Sónia Kristy Pinto Melo , e Silva Airton Pereira , Marmello Bárbara Oliveira , Teixeira Gerlinde Agate Platais Brasil
Published: February 2020

Food allergy is an IgE and or IgG immune-mediated reaction to food antigens. Knowledge of the allergenicity properties of proteins, how they react in the body and in diagnostic tests is necessary to adequately assess the allergenic potential of both natural foods and those produced through biotechnological processes. Thus, our aim was analyze the factors those influence the protein extraction of foods in terms of yield, allergenicity and sensitivity in immunoassays. Peanut proteins were extracted using 4 distinct extraction buffers (physiological saline, tris buffer, borate buffer with and without β-mercaptoethanol). The protein concentration of the obtained extracts was determined by the Lowry method. Polyacrylamide electrophoresis (SDS-PAGE) was used to compare the protein profile of each extract. Immunogenicity of each extract was verified by sensitizing two mouse strains (Balb/c and C57/BL6) with 100μg of the proteins, and the immunoreactivity was determined by ELISA. Our results show that extraction with the distinct buffers resulted in protein solutions with different yields and profiles. The antigenicity of the different extracts in a murine model of systemic immunization also demonstrated distinct patterns that varied depending on the extraction methods and mouse strain. The immunoreactivity varied in accordance to the protein extract used to coat the microtitration plates. In conclusion,the protein yield and profile in the extracts is critically influenced by the salt composition and pH of the extraction buffers. This in turn influences both in vivo immunogenicity and in vitro immunoreactivity.
Cooperation between CRISPR-Cas types enables adaptation in an RNA-targeting system
Authors: Hoikkala Ville , Ravantti Janne , Díez-Villaseñor César , Tiirola Marja , Conrad Rachel A. , McBride Mark J. , Sundberg Lotta-Riina
Published: February 2020

CRISPR-Cas immune systems adapt to new threats by acquiring spacers from invading nucleic acids such as phage genomes. However, some CRISPR-Cas loci lack genes necessary for spacer acquisition, despite apparent variation in spacer content between strains. It has been suggested that such loci may use acquisition machinery from co-occurring CRISPR-Cas systems. Here, using a lytic dsDNA phage, we observe spacer acquisition in the native host Flavobacterium columnare that carries an acquisition-deficient subtype VI-B locus and a complete subtype II-C locus. We characterize acquisition events in both loci and show that the RNA-targeting VI-B locus acquires spacers in trans using acquisition machinery from the DNA-targeting II-C locus. Our observations reinforce the concept of modularity in CRISPR-Cas systems and raise further questions regarding plasticity of adaptation modules.
Modulation of bacterial multicellularity via spatiotemporal polysaccharide secretion
Authors: Islam Salim T. , Alvarez Israel Vergara , Saïdi Fares , Giuseppi Annick , Vinogradov Evgeny , Morrone Castrese , Brasseur Gael , Sharma Gaurav , Benarouche Anaïs , Bridot Jean-Luc , Ravicoularamin Gokulakrishnan , Cagna Alain , Gauthier Charles , Singer Mitchell , Fierobe Henri-Pierre , Mignot Tâm , Mauriello Emilia M. F.
Published: February 2020

Abstract

The development of multicellularity is a key evolutionary transition allowing for differentiation of physiological functions across a cell population that confers survival benefits; among unicellular bacteria, this can lead to complex developmental behaviours and the formation of higher-order community structures. Herein, we demonstrate that in the social δ-proteobacteriumMyxococcus xanthus, the secretion of a novel secreted biosurfactant polysaccharide (BPS) is temporally and spatially modulated within communities, mediating swarm migration as well as the formation of multicellular swarm biofilms and fruiting bodies. BPS is a type IV pilus-inhibited acidic polymer built of randomly-acetylated β-linked tetrasaccharide repeats. Both BPS and the “shared good” EPS are produced by dedicated Wzx/Wzy-dependent polysaccharide assembly pathways distinct from that responsible for spore coat assembly. To our knowledge, such pathways have never-before been explicitly shown to synthesize a biosurfactant. Together, these data reveal the central role of secreted polysaccharides in the intricate behaviours coordinating bacterial multicellularity.