bluuebunny/crossref_metadata_2025 huggingface dataset:
Echocardiographic Evaluation of the Response to Prazosin Treatment in Scorpion Sting
Authors: Abdel Baseer Khaled A , Aboelela Mohamed Gamil , Qubaisy Heba M
Published: July 2020

Background

Scorpion envenomation is a major public health problem in children that can induce lethal neurological, respiratory and cardiovascular complications. We aimed to evaluate cardiovascular complications with a follow-up of envenomed children for 1 month for possibility of incomplete recovery.

Methods

This was a prospective study conducted for children who presented with scorpion sting to Emergency and Intensive Care units. Demographic, clinical and laboratory findings of patients were recorded. Cases with suspected clinical and electrocardiographic manifestations of myocarditis were subjected to bedside echocardiography with follow-up at the end of the first week and the first month.

Results

Scorpion sting cases presented to our hospital were 81 cases during 1-year study; of them, 17 cases were stable without systemic manifestations after 12 h observation and discharged. Sixty-four cases suffered systemic organic complications and needed ICU admission; their mean age was 11.52 ± 3.74 and 64% of them were males. Twenty-eight of admitted cases showed manifestations of myocarditis and by echocardiography, all of them had evidence of left ventricular dysfunction. On follow-up, there was significant improvement at the end of first week and complete improvement at the end of first month except three cases who died due to pulmonary edema and cardiogenic shock.

Conclusion

Acute toxic myocarditis is a common and an important cause of morbidity and mortality following scorpion envenomation that necessitates early and aggressive management. High index of suspicion, serial electrocardiogram monitoring and echocardiography are three integrative lines required to recognize this serious complication.

Lay summary

Acute toxic myocarditis is a common cause of morbidity and mortality following scorpion envenomation that necessitates rapid medical treatment. We aimed to evaluate cardiovascular complications after scorpion sting with a follow-up of envenomed children for 1 month for possibility of incomplete recovery. Tachycardia was the most frequent observed cardiac sign followed by hypotension, while the least was bradycardia and hypertension. All cases with manifestations suggestive of myocarditis were evaluated by bedside two-dimensional echocardiography and showed evidence of left ventricular dysfunction, that begin to regress within 1 week of treatment unless progressive pulmonary edema and resistant cardiogenic shock occurred. On follow-up for survivors, complete improvement at the end of first month was noticed. Clinical suspicion, serial ECG monitoring and echocardiography are required for rapid and early diagnosis. Early use of prazosin therapy can prevent long-term residual damage as evidenced by echocardiographic evaluation.
Continuous Quality Improvement of Writing Assignments: A Process for Faculty Development
Authors: Singleterry Lisa R. , Caulfield Susan
Published: July 2020

This article describes a four-step instructional design framework to assist nursing faculty with development of writing assignments. The framework encourages faculty to design assignments with a purpose, objectives, directions, and evaluation (PODE). Use of the PODE framework may reduce faculty frustration with students’ writing assignments and allow for continuous quality improvement of assignments and students’ writing skills. Faculty who have used the framework found it useful to improve development, assessment, and revision of course assignments, resulting in better work from students.
Using Learning Curves to Identify and Explain Growth Patterns of Learners in Bronchoscopy Simulation: A Mixed-Methods Study
Authors: Mema Briseida , Mylopoulos Maria , Tekian Ara , Park Yoon Soo
Published: July 2020

Purpose

Learning curves can illustrate how trainees acquire skills and the path to competence. This study examined the growth trajectories of novice trainees while practicing on a bronchoscopy virtual reality (VR) simulator compared with those of experts.

Method

This was a sequential explanatory mixed-methods design. Twenty pediatric subspecialty trainees and 7 faculty practiced with the VR simulator (October 2017 to March 2018) at the Hospital for Sick Children, Toronto, Canada. The authors examined the relationship between number of repetitions and VR outcomes and patterns of growth using a growth mixture modeling. Using an instrumental case study design, field notes and semistructured interviews with trainees and simulation instructor were examined to explain the patterns of growth. The authors used a constant comparative approach to identify themes iteratively. Team analysis continued until a stable thematic structure was developed and applied to the entire data.

Results

The growth mixture model identified 2 patterns of growth. A slower growth included learners that had inherent difficulty with the skill, did not integrate the knowledge of anatomy in simulation practice, and used the simulator for simple repetitive practice with no strategy for improvement in between trials. The faster growth included learners who used an adaptive expertise approach: integrating knowledge of anatomy, finding flexible solutions, and creating a deeper conceptual understanding.

Conclusions

The authors provide validity evidence for use of growth models in education and explain patterns of growth such as a “slow growth” with a mechanistic repetitive practice and a “fast growth” with adaptive expertise.
Update on noninfectious uveitis in children and its treatment
Authors: Maccora Ilaria , Sen Ethan S. , Ramanan Athimalaipet V.
Published: July 2020

Purpose of review

To give an overview of recently published articles covering risk factors, novel biomarkers and treatment for noninfectious uveitis in children.

Recent findings

In the last few years, several genetic markers, serum biomarkers, aqueous humor markers, tear biomarkers and clinical factors have been identified, which are associated with childhood noninfectious uveitis. We describe the most important reports in this field that may help to tailor the screening and monitoring of this population in the future and might become the target of novel therapies. The advances in the biologic therapy of paediatric uveitis, thanks to evidence provided by the SYCAMORE, ADJUVITE and APTITUDE trials, offer new possibilities for the treatment of patients who fail methotrexate with adalimumab and tocilizumab. We discuss the importance of comprehensive outcome measures as proposed by the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC).

Paediatric noninfectious uveitis is a sight-threatening condition and the identification of risk factors and novel biomarkers is critical for tailored management. Biologic therapies are revolutionizing the outcomes of patients resistant to conventional therapy. Increasing our knowledge of disease pathogenesis is crucial to improve targeting of screening to those at highest risk and stratification of treatments.
Epidemiology and outcomes of novel coronavirus 2019 in patients with immune-mediated inflammatory diseases
Authors: Gianfrancesco Milena , Yazdany Jinoos , Robinson Philip C.
Published: July 2020

Purpose of review

The novel coronavirus 2019 (COVID-19) pandemic is of special concern for patients with immune-mediated inflammatory disease (IMID) and those who care for them because of the potential for worse outcomes. This article analyzes peer-reviewed research on the epidemiology and outcomes of COVID-19 in those with IMID.

Recent findings

Published literature on approximately 1400 patients was included from rheumatology, gastroenterology, and dermatology. Data suggest that those who are older and have comorbidities have poorer outcomes. This is consistent with the reports from the general population of patients with COVID-19. Adjusted analyses from the largest published studies demonstrate independent effects of systemic glucocorticoids, as well as age and comorbidities with poorer COVID-19 outcomes (SECURE-IBD registry, n = 525; COVID-19 Global Rheumatology Alliance registry, n = 600); biologic or targeted synthetic disease-modifying antirheumatic drug therapy has not been associated with more severe outcomes. These early results will require validation in population-based studies as more data becomes available.

Current data suggest that similar to the general population, age, and comorbidities are risk factors for poorer COVID-19 outcomes in patients with IMID. Additional research is needed to quantify outcomes and risk across rheumatic disease types, comorbidities, and immunosuppressive drugs.
Does Main Curve Flexibility Affect Screw Insertion Accuracy Using a CT-based Navigation System in Adolescent Idiopathic Scoliosis Surgery?
Authors: Uehara Masashi , Takahashi Jun , Shimizu Masayuki , Ikegami Shota , Kuraishi Shugo , Oba Hiroki , Takizawa Takashi , Munakata Ryo , Hatakenaka Terue , Koseki Michihiko , Kato Hiroyuki
Published: July 2020

Study Design:

A retrospective single-center and single-surgeon study.

Objective:

This study investigated the screw perforation rate according to main curve flexibility in pedicle screw fixation using a computed tomography (CT) guidance for adolescent idiopathic scoliosis (AIS).

Summary of Background:

The authors have been using a CT-based navigation system during pedicle screw insertion for AIS to avoid serious neurovascular or visceral structure injury but suspect that high main curve flexibility may account for some breaches.

Data:

Seventy-two consecutive patients with AIS Lenke type 1 or 2 who had undergone pedicle screw fixation using a CT-based navigation system between February 2008 and April 2018 were retrospectively reviewed.

Materials and Methods:

The authors evaluated the perforation rate of pedicle screws inserted into the main thoracic curve between the upper-end and lower-end vertebrae for factors associated with screw violations using multivariate logistic regression mixed models.

Results:

A total of 723 pedicle screws were inserted into the T4–T12 vertebrae with the aid of CT-based navigation. The respective grade 3 perforation rates according to main curve flexibility were 0%–30%: 3.2%; 30%–55%: 1.1%; 55%–75%: 5.2%; and 75%–100%: 5.5%. Main curve flexibility of ≥55% was significantly associated with grade 3 screw perforations (P=0.02).

Conclusions:

Main curve flexibility of ≥55% was significantly related to screw violation in AIS surgery. Greater care is thus advised for screw insertion using CT navigation in AIS with main curve flexibility ≥55%.
Targeting defective DNA repair in prostate cancer
Authors: Carmichael Juliet , Maza Maria de los Dolores Fenor de la , Rescigno Pasquale , Chandran Khobe , de Bono Johann
Published: July 2020

Purpose of review

Prostate cancer is the second leading cause of cancer death in men. Characterization of the genomic landscape of prostate cancer has demonstrated frequent aberrations in DNA repair pathways, identifiable in up to 25% patients with metastatic disease, which may sensitize to novel therapies, including PARP inhibitors and immunotherapy. Here, we summarize the current clinical landscape and future horizons for targeting defective DNA repair pathways in PC.

Recent findings

Several clinical trials have demonstrated efficacy of different PARP inhibitors in metastatic castration-resistant prostate cancer (mCRPC), most pronounced in those with BRCA mutations. The PROfound trial is the first positive phase 3 biomarker-selected trial to demonstrate improved outcomes with a targeted treatment, Olaparib, in mCRPC. Whilst the Keynote-199 trial failed to demonstrate efficacy of immune-checkpoint inhibitor pembrolizumab in unselected mCRPC patients, there was evidence of response in those harbouring DNA repair defects.

These landmark trials represent a significant advance towards personalization of PC therapy. However, resistance remains inevitable and there is a lack of reliable predictive biomarkers to select patients for treatment. Characterization of resistance mechanisms, and validation of novel biomarkers is critical to maximize clinical benefit and inform novel treatment combinations to improve outcomes.
The role of myeloid-derived suppressor cells in hematologic malignancies
Authors: Gunes Emine Gulsen , Rosen Steven T. , Querfeld Christiane
Published: July 2020

Purpose of review

This article focuses on the immunosuppressive impact of myeloid-derived suppressor cells (MDSCs) and the potential clinical implications in hematological malignancies.

Recent findings

MDSCs play a critical role in the regulation of the immune response in cancer. They inhibit activation of adaptive immune response and as a result foster the growth of the malignancy. Recent studies have shown that MDSCs serve as prognostic biomarkers and as targets for cancer immunotherapy. Preclinical and clinical studies have identified new approaches to deplete MDSC populations and inhibit MDSC function with combination immunomodulatory therapies including chemotherapeutic agents with immune checkpoint-directed treatment.

A broad spectrum of publications indicate that direct targeting of MDSCs may abrogate their protumorigenic impact within the tumor microenvironment through activation of the adaptive immune response.
Penile Necrosis as a Presenting Sign of Purpura Fulminans Mimicking Fournier's Gangrene
Authors: Caputo Valentina , Bonoldi Emanuela , Rongioletti Franco
Published: July 2020

We report the case of a 63-year-old white man who, 3 days after stent removal of endoscopic drainage of pancreatic cysts, developed a penile necrosis due to purpura fulminans (PF) that has been misdiagnosed as Fournier's gangrene. Penile necrosis was rapidly followed by a lethal multiorgan failure due to disseminated intravascular coagulopathy (DIC), triggered by the subsequent development of a severe acute pancreatitis. PF describes a rare syndrome involving intravascular thrombosis and hemorrhagic infarction of the skin. Although reports of penile necrosis secondary to various causes are documented in the literature, penile necrosis secondary to PF in the setting of acute pancreatitis is a rare event. Histopathologic studies of the skin showing an occlusive nonvasculitic vasculopathy are the first step to achieve an accurate diagnosis.
The Association of Febuxostat Compared With Allopurinol on Blood Pressure and Major Adverse Cardiac Events Among Adult Patients With Hyperuricemia: A Meta-analysis
Authors: Barrientos-Regala Marie , Macabeo Renelene A. , Ramirez-Ragasa Rosemarie , Pestaño Noemi S. , Punzalan Felix E. R. , Tumanan-Mendoza Bernadette , Castillo Rafael R.
Published: July 2020

Increased uric acid levels have been known to be associated with different cardiovascular and renal diseases. Over the past few years, several studies have examined the role of urate-lowering therapy (ULT) in hypertension and major adverse cardiac events (MACE) and suggest a potential role of elevated serum uric acid as an independent cardiovascular risk factor. This meta-analysis was done to determine the association of 2 ULTs commonly used in clinical practice (febuxostat vs. allopurinol) on hypertension and MACE and resolve the conflicting results of the outcomes of earlier studies. Randomized controlled trials comparing febuxostat versus allopurinol published with outcomes on blood pressure, all-cause mortality, myocardial infarction (MI), and stroke were searched through PubMed, Google Scholar, and Cochrane database. A total of 10 studies were subsequently included in the meta-analysis. Pooled analysis of the mean differences (MD) were done for the outcomes on blood pressure (systolic and diastolic) and risk ratios (RRs) for the outcomes on MACE with corresponding 95% confidence intervals (CIs). Pooled analysis of studies on hyperuricemic patients showed that febuxostat 40 mg has no significant difference compared with allopurinol 100/300 mg with respect to diastolic (MD, −0.56 with 95% CI of −4.28 to 3.15) and systolic blood pressure (MD, 0.30 with 95% CI of −3.33 to 3.93). No significant differences were also noted on all-cause mortality (RR, 1.18 with 95% CI of 0.99–1.41), MI (RR, 0.92 with 95% CI of 0.72–1.18), and stroke (RR, 1.05 with 95% CI of 0.77–1.43). The results of this meta-analysis showed that the 2 ULTs (febuxostat vs. allopurinol) have no significant association with respect to blood pressure among adult patients with hyperuricemia. No significant association was also noted of either ULT with all-cause mortality, MI, and stroke.
Diabetes and CYP2C19 Polymorphism Synergistically Impair the Antiplatelet Activity of Clopidogrel Compared With Ticagrelor in Percutaneous Coronary Intervention–treated Acute Coronary Syndrome Patients
Authors: Mohareb Mina W. , AbdElghany Mohamed , Zaki Hala F. , El-Abhar Hanan S.
Published: July 2020

Diabetes and CYP2C19 loss of function (LOF) alleles are associated with the variable antiplatelet activity of the prodrug clopidogrel. We conducted a randomized trial (NCT03613857) to compare the combined and individualized effects of diabetes and CYP2C19 polymorphisms on the antiplatelet reactivity of clopidogrel versus ticagrelor in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Patients (948, 1 year follow-up 943) were randomly allocated in a 1:1 ratio to receive either clopidogrel or ticagrelor, after PCI; patients were subdivided into 8 subgroups according to the diabetes and/or CYP2C19 allele status. The study outcomes were recurrent ACS, maximum platelet aggregation (MPA), high platelet reactivity index (PRI), and incidence of major bleeding events. Diabetic patients with LOF alleles taking clopidogrel had the highest recurrent ACS rate (6 of 33 patients) versus all other study groups (P < 0.05). However, both drugs had similar proportions of recurrent ACS in all other subgroups. Similarly, both PRI and MPA were significantly higher in the diabetic patients having LOF alleles and receiving clopidogrel versus all their study groups (P < 0.05). Nevertheless, ticagrelor caused higher rates of major bleeding versus clopidogrel (P < 0.001). PCI-treated ACS patients with diabetes and CYP2C19 LOF alleles are at a higher risk of recurrent ACS and high PRI/MPA, when treated with clopidogrel versus ticagrelor, but almost comparable outcomes are recorded in the absence of 1 or the 2 risk factors.
Cochlear Implantation in Patients With Menière's Disease: Does Disease Activity Affect the Outcome?
Authors: Kocharyan Armine , Mark Michelle E. , Ascha Mustafa S. , Murray Gail S. , Manzoor Nauman F. , Megerian Cliff , Mowry Sarah E. , Semaan Maroun T.
Published: July 2020

Objective:

Menière's disease (MD) is characterized by episodes of vertigo, tinnitus, and sensorineural hearing loss. In the setting of bilateral deafness due to MD alone or contralateral pathology, cochlear implantation (CI) improves hearing. Active MD is characterized by fluctuating auditory symptoms and vertigo; whereas remittance of vertiginous symptoms and severe, permanent sensorineural hearing loss characterizes the inactive disease state. This study evaluates outcomes for MD patients compared with the general CI population and assesses if disease activity affects implant outcomes.

Study Design:

Retrospective chart review.

Setting:

Tertiary referral center.

Patients:

Twenty-four patients with MD that received CI (7 active, 16 inactive, and 1 Probable Menière's), and 24 age-matched controls.

Interventions:

Cochlear implantation.

Main Outcome Measures:

Word Recognition Score, Sentence Recognition Score (SRS), and Speech Reception Threshold.

Results:

Best-aided preoperative and postoperative audiometric data were compared per ear between MD patients and controls and stratified by disease status using descriptive statistics with mixed-effects modeling. Patients with MD derived significantly more benefit from CI than controls when comparing differences between preoperative and postoperative levels for Word Recognition Score (12.2%,p = 0.0236), SRS (12.8%,p = 0.0375), and Speech Reception Threshold (−14.4 dB,p = 0.0188). Active disease status does not negatively impact CI outcomes and patients with active MD may benefit from greater gains in SRS (23.5%,p = 0.0107).

Conclusions:

CI provides greater gains in functional hearing for patients with MD compared with age-matched controls. Patients with active MD seem to perform better with respect to SRS following CI than patients with inactive status.
Effects of a personalized physical exercise program in peripheral and central blood pressure in community dwelling old hypertensive adults: the AGA@4life intervention model
Authors: Pereira Telmo , Cipriano Inês
Published: July 2020

We aimed at testing the effect of a tailored physical exercise intervention program on brachial and central blood pressure (bBP and cBP, respectively) in a group of hypertensive old adults. Thirty-three participants (mean age: 82 ± 9 years) were divided into two groups (intervention group and control group) according to their adherence to the physical training program. The exercise program included aerobic and strength components, prescribed in a personalized approach, and implemented under a strict control of two experienced professionals. An oscillometric-based device was used to measure bBP and cBP, both at baseline ant 3 months after the intervention period. The groups had similar clinical and demographic characteristics at baseline. No significant changes were observed in any of the considered endpoints in the control group. Conversely, a significant reduction was depicted in the intervention group, for both bBP and cBP. The results demonstrate that physical exercise prescribed in a tailored approach is an effective nonpharmacological tool to reduce pBP and cBP in older adults.
Natural Adhesion Blepharoplasty Technique
Authors: Jung Gyu Sik
Published: July 2020

Nonincisional blepharoplasty is widely practiced to make natural double eyelids. However, this method has the disadvantage of the double fold loosening compared to incisional blepharoplasty. Many researchers have proposed a method of nonincisional blepharoplasty with lower risk of loosening. The authors innovated the method to induce spontaneous adhesion in a nonincisional blepharoplasty with induction of partial linear adhesions, and, therefore, lowering the risk of suture loosening. While performing this procedure, the orbicularis oculi muscle and the levator palpebrae muscle were partially incised through eight tiny incisions to induce adhesion, and the double eyelid was made with the nonincisional continuous suture technique. This study included 99 patients who underwent natural adhesion blepharoplasty technique between January and December 2018. After 1 year of follow-up, no double eyelid loosening was observed. Natural adhesion blepharoplasty is simple technique to create natural-looking results and a durable double fold with satisfactory aesthetic results.
Long-term Outcomes Following Primary Closure of Common Bile Duct Following Laparoscopic Common Bile Duct (CBD) Exploration: Experience of 355 Cases at a Tertiary Care Center
Authors: Asuri Krishna , Bansal Virinder K. , Bagaria Vivek , Prajapati Omprakash , Kumar Subodh , Ramachandran Rashmi , Garg Pramod , Misra Mahesh C.
Published: July 2020

Introduction:

Primary closure of common bile duct (CBD) after laparoscopic common bile duct exploration (LCBDE) is now becoming the preferred technique for closure of choledochotomy. Primary CBD closure not only circumvents the disadvantages of an external biliary drainage but also adds to the advantage of LCBDE. Here, we describe our experience of primary CBD closure following 355 cases of LCBDE in a single surgical unit at a tertiary care hospital.

Materials and Methods:

All patients undergoing LCBDE in a single surgical unit were included in the study. Preoperative and intraoperative parameters including the technique of CBD closure were recorded prospectively. The postoperative recovery, complications, hospital stay, antibiotic usage, and postoperative intervention, if any, were also recorded.

Results:

Three hundred fifty-five LCBDEs were performed from April 2007 to December 2018, and 143 were post-endoscopic retrograde cholangiopancreatography failures. The overall success rate was 91.8%. The mean operative time was 98±26.8 minutes (range, 70 to 250 min). Transient bile leak was seen in 10% of patients and retained stones in 3 patients. Two patients required re-exploration and 2 patients died in the postoperative period. Follow-up ranged from 6 months to 10 years, with a median follow-up of 72 months. No long-term complications such as CBD stricture or recurrent stones were noted.

Conclusions:

Primary closure of CBD after LCBDE is safe and associated with minimal complications and no long-term problems. The routine use of primary CBD closure after LCBDE is recommended based on our experience.
FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs
Authors: Griffith Billie G. C. , Upstill-Goddard Rosanna , Brunton Holly , Grimes Graeme R. , Biankin Andrew V. , Serrels Bryan , Byron Adam , Frame Margaret C.
Published: July 2020

Focal adhesion kinase (FAK) localizes to focal adhesions and is overexpressed in many cancers. FAK can also translocate to the nucleus, where it binds to, and regulates, several transcription factors, including MBD2, p53 and IL-33, to control gene expression by unknown mechanisms. We have used ATAC-seq to reveal that FAK controls chromatin accessibility at a subset of regulated genes. Integration of ATAC-seq and RNA-seq data showed that FAK-dependent chromatin accessibility is linked to differential gene expression, including of the FAK-regulated cytokine and transcriptional regulator interleukin-33 (Il33), which controls anti-tumor immunity. Analysis of the accessibility peaks on theIl33gene promoter/enhancer regions revealed sequences for several transcription factors, including ETS and AP-1 motifs, and we show that c-Jun, a component of AP-1, regulatesIl33gene expression by binding to its enhancer in a FAK kinase-dependent manner. This work provides the first demonstration that FAK controls transcription via chromatin accessibility, identifying a novel mechanism by which nuclear FAK regulates biologically important gene expression.
TATA and paused promoters active in differentiated tissues have distinct expression characteristics
Authors: Ramalingam Vivekanandan , Natarajan Malini , Johnston Jeff , Zeitlinger Julia
Published: July 2020

Core promoter types differ in the extent to which RNA polymerase II (Pol II) pauses after initiation, but how this difference affects their tissue-specific gene expression characteristics is not well understood. While promoters with Pol II pausing elements are active at all stages of development, TATA promoters are highly active in differentiated tissues. We therefore used a genomics approach on late-stageDrosophilaembryos to analyze the properties of promoter types. Using tissue-specific Pol II ChIP-seq, we found that paused promoters have high levels of paused Pol II throughout the embryo, even in tissues where the gene is not expressed, while TATA promoters only show Pol II occupancy when the gene is active. This difference between promoter types is associated with different chromatin accessibility in ATAC-seq data and different expression characteristics in single-cell RNA data. The results suggest that promoter types have optimized different promoter properties: paused promoters show more consistent expression when active, while TATA promoters have lower background expression when inactive. We propose that tissue-specific effector genes have evolved to use two different strategies for their differential expression across tissues.
Organizational culture, quality of care and leadership style in government general hospitals in Kuwait: a multimethod study
Authors: ALFadhalah Talal , Elamir Hossam
Published: July 2020

Purpose

To investigate the organizational culture, assess the quality of care, and measure their association with a transformational/transactional leadership style in six hospitals.

Materials and methods

We used cross-sectional and retrospective quantitative approaches in government-sponsored secondary-care hospitals. A sample of 1,626 was drawn from a frame of 9,863 healthcare workers in six hospitals. Followers were surveyed using the Multifactor Leadership Questionnaire and the Organizational Description Questionnaire. We reviewed and analyzed one year (2012) of quarterly and annual quality indicators from the hospitals. Data were analyzed using suitable statistical analyses.

Results

We collected 1,626 responses from six hospitals. 66.4% to 87.1% of participants in each hospital identified their hospital’s organizational culture as transformational, whereas 41 out of 48 departments were identified as having a transformational culture. The percentage of participants at each hospital rating their leader and organizational culture as transformational ranged from 60.5% to 80.4%. The differences between leadership style and organizational culture were statistically significant for four of the hospitals. For most of the quality indicators, there was a positive, but nonsignificant, correlation with leadership style.

Conclusion

Leaders define and influence organizational culture. The prevailing transformational leadership style creates and maintains a transformational organizational culture. The effect of transformational leadership on the quality of care delivered by the organization was measured in this study, and showed a positive and nonsignificant relationship between generic quality indicators and the transformational style.
SARS-COV-2 THREE FORCING SEASONALITIES: POLICIES, ENVIRONMENT AND URBAN SPACES
Authors: Telles Charles Roberto
Published: July 2020

This research investigated if pandemic of SARS-COV-2 follows the Earth seasonality ε comparing countries cumulative daily new infections incidence over Earth periodic time of interest for north and south hemisphere. It was found that no seasonality in this form ε occurs as far as a seasonality forcing behavior ε′ assumes most of the influence in SARS-COV-2 spreading patterns. Putting in order ε′ of influence, there were identified three main forms of SARS-COV-2 of transmission behavior: during epidemics growth, policies are the main stronger seasonality forcing behavior of the epidemics followed by secondary and weaker environmental and urban spaces driving patterns of transmission. At outbreaks and control phase, environmental and urban spaces are the main seasonality forcing behavior due to policies/ALE limitations to address heterogeneity and confounding scenario of infection. Finally regarding S and R compartments of SIR model equations, control phases are the most reliable phase to predictive analysis.

These seasonality forcing behaviors cause environmental driven seasonality researches to face hidden or false observations due to policy/ALE interventions for each country and urban spaces characteristics. And also, it causes policies/ALE limitations to address urban spaces and environmental seasonality instabilities, thus generating posterior waves or uncontrolled patterns of transmission (fluctuations).

All this components affect the SARS-COV-2 spreading patterns simultaneously being not possible to observe environmental seasonality not associated intrinsically with policies/ALE and urban spaces, therefore conferring to these three forms of transmission spreading patterns, specific regions of analysis for time series data extraction.
Reconstitution of human kinetochore in mitotic cell extracts reveals permitted and restricted assembly steps
Authors: Tarasovetc Ekaterina V. , Allu Praveen Kumar , Cheeseman Iain M. , Black Ben E. , Grishchuk Ekaterina L.
Published: July 2020

Assembly of a functional kinetochore is critical for accurate chromosome segregation. Hierarchical recruitment of soluble components during kinetochore assembly is a highly regulated mitotic event, but the underlying steps are not well understood. In yeast andXenopusegg extracts, soluble kinetochore components can spontaneously assemble into microtubule-binding subcomplexes. Although the molecular interactions among specific kinetochore components are evolutionary conserved in eukaryotes, it remains unclear whichde novoassembly steps are permitted in extracts of mitotic human cells. By analyzing the recruitment of GFP-fused kinetochore proteins from human mitotic cell extracts to inner kinetochore components immobilized on microbeads, we reconstructed the interaction between CENP-C and CENP-A–containing nucleosomes. However, subsequent phospho-dependent binding of the Mis12 complex was less efficient, whereas binding of the Ndc80 complex was inhibited. Consistently, the microtubule-binding activity of native kinetochore components, as well as those assembled using a combination of native and recombinant human proteins, was weaker than that of recombinant Ndc80 complex alone. Such inhibitory mechanisms that prevent interactions between different kinetochore components are likely to guard against spurious formation of kinetochores in the cytosol of mitotic human cells, and imply existence of specific regulatory mechanisms that permit these interactions at the assembling kinetochore.
AraC mutations that suppress inactivating mutations in the C-terminal domain of the RpoA subunit ofEscherichia coliRNA polymerase
Authors: Belin Dominique , Silva Filo
Published: July 2020

InE. coli, transcriptional activation is often mediated by the C-terminal domain of RpoA, the α subunit of RNA polymerase. Mutations that prevent activation of the arabinose PBADpromoter are clustered in a small region of the α–CTD domain around K271. To determine the target(s) of RpoA in the PBADpromoter, we have isolated suppressors ofrpoAα–CTD mutations. The suppressors map to the N-terminal domain of AraC, the main transcriptional regulator ofaragene expression. No mutation was found in the large DNA regulatory region betweenaraCand PBAD, suggesting that, in this system, RpoA does not activate transcription through its direct DNA binding. One class ofaraCmutations result in substitutions in the core of the N-terminal domain suggesting that they may affect its conformation. Another class of suppressors define genetically a domain that potentially interacts with the C-terminal domain of RpoA. Surprisingly, inrpoA+strains lacking CRP, thearaCmutations largely restore arabinose gene expression, suggesting that they somehow strengthen the AraC:α–CTD interaction. Thus, the N-terminal domain of AraC exhibits at least three activities: dimerization, arabinose binding and transcriptional activation via RpoA.

Importance

Gene expression is most often controlled at the level of transcription by regulators that interact with RNA polymerase. The C-terminal domain ofEscherichia coliRpoA is attached to the core enzyme by a flexible linker and serves as a hub that interacts with many regulators and even with DNA sites to activate transcription. Mutations in a RpoA subdomain interfere with activation of the main arabinose promoter by AraC, the regulator that either activates or represses expression of the arabinose operons. We define here genetically the target of RpoA in the main arabinose promoter. Suppressors of most RpoA mutations map to the N-terminal domain of AraC that promotes its dimerization and binds to arabinose, the inducer. Thus, our results identify a third function for this AraC domain. Some suppressors define a potential binding site for RpoA, while others, at internal residues, probably affect the conformation of the AraC domain.
Fruit presence induces polar auxin transport in citrus and olive stem and represses hormone release from the bud
Authors: Haim Dor , Shalom Liron , Simhon Yasmin , Shlizerman Lyudmila , Kamara Itzhak , Morozov Michael , Albacete Moreo Alfonso Ant , Rivero Rosa M , Sadka Avi
Published: July 2020

In many fruit trees, heavy fruit load in one year reduces flowering in the following year, creating a biennial fluctuation in yield termed alternate bearing (AB). In subtropical trees, where flowering induction is mostly governed by the accumulation of cold hours, fruit load is thought to generate a signal (AB signal) that blocks the perception of the cold induction. Fruit removal during a heavy-fruit-load year (On-Crop) is effective at inducing flowering only if performed one to a few months prior to onset of the flowering-induction period. We previously showed that following fruit removal, content of the auxin indoleacetic acid (IAA) in citrus buds is reduced, suggesting that the hormone plays a role in the AB signal. Here, we demonstrate that fruit presence generates relatively strong polar auxin transport (PAT) in citrus and olive stems. Upon fruit removal, PAT is reduced and allows auxin release from the bud. Furthermore, using immunolocalization, hormone and gene expression analyses, we show that in citrus, IAA level in the bud and, specifically, in the apical meristem is reduced upon fruit removal. Overall, our data provide support for the notion that fruit presence generates an auxin signal in the bud which may affect flowering induction.

HIGHLIGHTS

Heavy fruit load can reduce flowering intensity the following year. Fruit presence, inducing polar auxin transport in stems and inhibiting auxin release from buds, may be a fruit-load signal.
Vaccinia virus hijacks ESCRT-mediated multivesicular body formation for virus egress
Authors: Huttunen Moona , Yakimovich Artur , White Ian J. , Kriston-Vizi Janos , Martin-Serrano Juan , Sundquist Wesley I. , Mercer Jason
Published: July 2020

Unlike most enveloped viruses, poxvirus egress is a complex process whereby cytoplasmic single membrane-bound virions are wrapped in a cell-derived double membrane. These triple membrane-bound particles, termed intracellular enveloped virions (IEVs), are then released from infected cells by fusion. While the wrapping double membrane is thought to be derived from virus-modified trans-Golgi or early endosomal cisternae, the cellular factors that regulate virus wrapping remain largely undefined. To identify novel cell factors required for this process the prototypic poxvirus, vaccinia virus (VACV), was subjected to a high-throughput RNAi screen directed against cellular membrane trafficking proteins. Focusing on the endosomal sorting complexes required for transport (ESCRT), we demonstrate that ESCRT-III and VPS4 are required for packaging of virus into multivesicular bodies (MVBs). EM-based characterization of these MVB-IEVs showed that they account for half of IEV production indicating that MVBs serve as a second major source of VACV wrapping membrane. These data support a model whereby, in addition to cisternae-based wrapping, VACV hijacks ESCRT-mediated MVB formation to facilitate virus egress and spread.
The diagnostic value of RASSF1A promoter methylation in prostate cancer: A systematic review and meta-analysis
Authors: Li Su-Liang , Li Ye-Xing , Ye Yun , Yuan Xiao-Hua , Wang Jian-Jun , Yan Hong-Lin
Published: July 2020

Background

RASSF1A promoter methylation is consistent with clinicopathological data and has good accuracy in distinguishing tumors. However, the diagnostic parameters vary among previous studies. A systematic review was conducted to explore the diagnostic value of RASSF1A promoter methylation in prostate cancer.

Methods

A comprehensive search of the literature in the PubMed, Medline, Cochrane Library, Embase and ISI Web of Science databases up to May 21, 2020 was performed. STATA software version 12.0 and Meta-disc version 1.4 were used to analyze the data.

Results

The pooled sensitivity was 0.64 (95% CI 0.61–0.66), the pooled specificity was 0.80 (95% CI 0.77–0.83), the PLR was 3.82 (95% CI 1.96–7.44), and the NLR was 0.29 (95% CI 0.16–0.52). Furthermore, the pooled DOR of RASSF1A promoter methylation for prostate cancer was 13.08 (95% CI: 6.56–26.08). The area under the summary ROC curve was 0.87 (95% CI: 0.84–0.90). The results of the meta-regression suggested that heterogeneity was mainly derived from publication year. Fagan’s nomogram showed that the predictive accuracy was increased significantly by detecting RASSF1A promoter methylation for diagnosing prostate cancer.

Conclusion

This meta-analysis suggests that detection of the RASSF1A promoter methylation status can be used for the diagnosis of PCa. In the future, further analyses and studies of larger sample sizes in large centers are needed to confirm our conclusion.
On the Emergence of P-Loop NTPase and Rossmann Enzymes from a Beta-Alpha-Beta Ancestral Fragment
Authors: Longo Liam M. , Jabłońska Jagoda , Vyas Pratik , Kanade Manil , Kolodny Rachel , Ben-Tal Nir , Tawfik Dan S.
Published: July 2020

Dating back to the last universal common ancestor (LUCA), the P-loop NTPases and Rossmanns now comprise the most ubiquitous and diverse enzyme lineages. Intriguing similarities in their overall architecture and phosphate binding motifs suggest common ancestry; however, due to a lack of sequence identity and some fundamental structural differences, these families are considered independent emergences. To address this longstanding dichotomy, we systematically searched for ‘bridge proteins’ with structure and sequence elements shared by both lineages. We detected homologous segments that span the first βαβ segment of both lineages and include two key functional motifs: (i) a phosphate binding loop – the ‘Walker A’ motif of P-loop NTPases or the Rossmann equivalent, both residing at the N-terminus of α1; and (ii) an Asp at the tip of β2. The latter comprises the ‘Walker B’ aspartate that chelates the catalytic metal in P-loop NTPases, or the canonical Rossmann β2-Asp that binds the cofactor’s ribose moiety. Tubulin, a Rossmann GTPase, demonstrates the potential of the β2-Asp to take either one of these two roles. We conclude that common P-loops/Rossmann ancestry is plausible, although convergence cannot be completely ruled out. Regardless, both lineages most likely emerged from a polypeptide comprising a βαβ segment carrying the above two functional motifs, a segment that comprises the core of both enzyme families to this very day.
Optimizing the use of gene expression data to predict plant metabolic pathway memberships
Authors: Wang Peipei , Moore Bethany M. , Uygun Sahra , Lehti-Shiu Melissa D. , Barry Cornelius S. , Shiu Shin-Han
Published: July 2020

Plant metabolites produced via diverse pathways are important for plant survival, human nutrition and medicine. However, the pathway memberships of most plant enzyme genes are unknown. While co-expression is useful for assigning genes to pathways, expression correlation may exist only under specific spatiotemporal and conditional contexts. Utilizing >600 expression values and similarity data combinations from tomato, three strategies for predicting membership in 85 pathways were explored: naive prediction (identifying pathways with the most similarly expressed genes), unsupervised and supervised learning. Optimal predictions for different pathways require distinct data combinations that, in some cases, are indicative of biological processes relevant to pathway functions. Naive prediction produced higher error rates compared with machine learning methods. In 52 pathways, unsupervised learning performed better than a supervised approach, which may be due to the limited availability of training data. Furthermore, using gene-to-pathway expression similarities led to prediction models that outperformed those based simply on gene expression levels. Our study highlights the need to extensively explore expression-based features and prediction strategies to maximize the accuracy of metabolic pathway membership assignment. We anticipate that the prediction framework outlined here can be applied to other species and also be used to improve plant pathway annotation.
Presenilin-deficient neurons and astrocytes display normal mitochondrial phenotypes
Authors: Contino Sabrina , Vrancx Céline , Suelves Nuria , Vadukul Devkee M. , Payen Valery L. , Stanga Serena , Bertrand Luc , Kienlen-Campard Pascal
Published: July 2020

Presenilins 1 and 2 (PS1 and PS2) are predominantly known as the catalytic subunits of the γ-secretase complex which generates the amyloid-β (Aβ) peptide, the major constituent of the senile plaques found in the brain of Alzheimer’s disease (AD) patients. Apart from their role in γ-secretase activity, a growing number of cellular functions have been recently attributed to PSs. They are involved in synaptic transmission, endo-lysosomal function and calcium homeostasis. PSs were also found to be enriched in mitochondria-associated membranes (MAMs) where mitochondria and endoplasmic reticulum (ER) interact. PS2 was more specifically reported to regulate calcium shuttling between the ER and mitochondria by controlling the formation of functional MAMs through its interaction with the Mitofusin2 protein. We have previously demonstrated that the absence of PS2 (PS2KO) alters mitochondrial morphology and function. Indeed, a PS2KO cell line showed reduced mitochondrial respiration along with disrupted mitochondrial cristae and increased glycolysis. This phenotype is restored by the stable re-expression of human PS2. Still, all these results were obtained in immortalized Mouse Embryonic Fibroblasts (MEF) and one bottom-line question is to know whether these observations hold true for the Central Nervous System (CNS) cells, and in particular neurons and astrocytes. To that end, we carried out primary PS1KO, PS2KO and PS1/PS2KO (PSdKO) neuronal and astrocyte cultures. All the conditions were obtained in the same litter by crossing PS2 heterozygous and PS1 floxed (PS2+/−; PS1flox/flox) animals. Indeed, contrary to PS2KO mice, PS1KO are not viable and therefore require the use of the Cre-LoxP system to achieve gene deletionin vitro. Strikingly, we did not observe any mitochondrial phenotype in PS1KO, PS2KO or PSdKO primary cultures. Mitochondrial respiration and membrane potential were similar in all models, as were the glycolytic flux and NAD+/NADH ratio. We further investigated the discrepancies between these results and the ones previously reported in the MEF PS2KO cell line by analyzing PS2KO primary fibroblasts. No mitochondrial dysfunction was observed in this model, in line with observations in PS2KO primary neurons and astrocytes. These results indicate that the mitochondrial phenotype observed in immortalized PS2-deficient cell lines cannot be extrapolated to primary neurons, astrocytes and even to primary fibroblasts. The PS-dependent mitochondrial phenotype reported so far might be the consequence of a cell immortalization process and, therefore, should be critically reconsidered regarding its relevance to AD.