bluuebunny/crossref_metadata_2025 huggingface dataset:
A pragmatic randomized controlled trial of a cardiac hospital-to-home transitional care program in a Singapore academic medical center
Authors: Chen Yanying , Tan Yi Jin , Sun Ya , Chua Cheng Zhan , Yoo Jeffrey Kwang Sui , Wong Shing Hei , Chen Helen , Meng Wong John Chee , Phan Phillip
Published: April 2020

Background

Rehospitalizations are common in healthcare. They are costly for hospitals and patients and a substantial percentage are preventable, partly because hospital-to-community transitions are often unmanaged or poorly managed. In this study, we conducted a pragmatic randomized, controlled trial to evaluate the effectiveness of a new nurse–practitioner-led transitional care program called CareHub, piloted in Singapore’s National University Hospital.

Methods

Study population included all eligible cardiac patients admitted between July 2016 and November 2016. Patients were followed for six months post-discharge. Primary outcomes other than emergency department visits were all cardiac-related: number of readmissions, specialist visits, emergency department visits, and total days readmitted. Secondary outcomes: variables related to quality of life and transitional care. Regression analyses were used to estimate the intent-to-treat effect of CareHub and explore treatment heterogeneity.

Results

CareHub reduced the mean number of unplanned readmissions by 0.23 (a 39% reduction relative to control mean of 0.60 unplanned readmissions, p < 0.05), mean number of all readmissions by 0.20 (31% reduction relative to control mean of 0.63 readmissions, p = 0.10), mean number of total unplanned days in hospital by 2.2 (56% reduction relative to control mean of 4.0 days, p < 0.05), mean number of total days in hospital by 2.0 (42% reduction relative to control mean of 4.3 days, p < 0.10). Treatment effects varied by pre-admission health and socio-economic status.

Conclusion

A carefully designed protocolized cardiac hospital-to-home transition program can reduce resource utilization while improving quality of life.
Medical accidents: A Socratic resolution?
Authors: Feeny Charles , Baker Gus , Irving Sam
Published: April 2020

Whilst medical accidents and adverse events clearly have to be the subject of response and redress for individuals who have suffered injury, the current approach to such accidents and events has developed in a piecemeal way. We argue that the various processes involved in such response and redress are outmoded and there is a lack of a clear overview, in particular in terms of promoting better clinical management and less psychological impact on the victim. The current effect of clinical negligence litigation produces adverse outcomes in terms of a patient's safety and the psychological wellbeing of victims. The time has come for an overall approach to be considered, which we suggest should be holistic and which would result in positive outcomes for the NHS and its patients.
Practical limitations of earthquake early warning
Authors: Wald David J
Published: April 2020

Earthquake early warning (EEW) entails detection of initial earthquake shaking and rapid estimation and notification to users prior to imminent, stronger shaking. EEW (ShakeAlert Phase 1, version 2.0) went operational in California in October 2019 and is coming to the rest of the U.S. West Coast. But what are the technical and social challenges to delivering actionable information on earthquake shaking before it arrives? Although there will be tangible benefits, there are also limitations. Basic seismological principles, alert communication challenges, and potential response actions, as well as substantial lessons learned from the use of EEW in Japan, point to more limited opportunities to warn and protect than perhaps many expect. This is in part because potential warning times vary by region and are influenced by tectonic environment, hypocentral depth, and the fault’s proximity to the alert user. For the U.S. West Coast, particularly for crustal earthquakes, warning times are shorter—and possible mitigation actions are likely to be less effective—than often maintained. Nevertheless, EEW is an additional arrow in the quiver of earthquake information tools available in the service of earthquake risk reduction. What is called for, then, is transparency and balance in the EEW discussion: along with its potential, the acknowledgment of EEW’s inherent and practical limitations is needed. Recognizing these limitations could, in fact, make EEW implementation more successful as part of a holistic earthquake mitigation strategy, where its role among other earthquake information tools is quite natural.
Plasma microparticles of sickle patients during crisis or taking hydroxyurea modify endothelium inflammatory properties
Authors: Garnier Yohann , Ferdinand Séverine , Garnier Marie , Cita Kizzy-Clara , Hierso Régine , Claes Aurélie , Connes Philippe , Hardy-Dessources Marie-Dominique , Lapouméroulie Claudine , Lemonne Nathalie , Etienne-Julan Maryse , El Nemer Wassim , Romana Marc
Published: April 2020

Microparticles (MPs) are submicron extracellular vesicles exposing phosphatidylserine (PS), detected at high concentration in the circulation of sickle cell anemia (SS) patients. Several groups studied the biological effects of MPs generated ex vivo. Here, we analyzed for the first time the impact of circulating MPs on endothelial cells (ECs) from 60 sickle cell disease (SCD) patients. MPs were collected from SCD patients and compared with MPs isolated from healthy individuals (AA). Other plasma MPs were purified from SS patients before and 2 years after the onset of hydroxyurea (HU) treatment or during a vaso-occlusive crisis and at steady-state. Compared with AA MPs, SS MPs increased EC ICAM-1 messenger RNA and protein levels, as well as neutrophil adhesion. We showed that ICAM-1 overexpression was primarily caused by MPs derived from erythrocytes, rather than from platelets, and that it was abolished by MP PS capping using annexin V. MPs from SS patients treated with HU were less efficient to induce a proinflammatory phenotype in ECs compared with MPs collected before therapy. In contrast, MPs released during crisis increased ICAM-1 and neutrophil adhesion levels, in a PS-dependent manner, compared with MPs collected at steady-state. Furthermore, neutrophil adhesion was abolished by a blocking anti–ICAM-1 antibody. Our study provides evidence that MPs play a key role in SCD pathophysiology by triggering a proinflammatory phenotype of ECs. We also uncover a new mode of action for HU and identify potential therapeutics: annexin V and anti–ICAM-1 antibodies.
IVMP+IVIG raises platelet counts faster than IVIG alone: results of a randomized, blinded trial in childhood ITP
Authors: Carcao Manuel , Silva Mariana , David Michele , Klaassen Robert J. , Steele MacGregor , Price Victoria , Wakefield Cindy , Kim Lussia , Stephens Derek , Blanchette Victor S.
Published: April 2020

Children with immune thrombocytopenia (ITP) rarely suffer from life-threatening bleeds (eg, intracranial hemorrhage). In such settings, the combination of IV methylprednisolone (IVMP) with IV immune globulin (IVIG) is used to rapidly increase platelet counts (PCs). However, there are no controlled data to support using combination therapy over IVIG alone. We conducted a randomized, double-blind, placebo-controlled study to evaluate the rapidity of the PC increment and associated adverse events (AEs) between 2 regimens: A (IV placebo) and B (IVMP 30 mg/kg), both given over 1 hour, followed in both cases by IVIG (Gamunex 10%) 1 g/kg over 2-3 hours in children 1-17 years old with primary ITP and PCs <20 × 109/L in whom physicians had decided to treat with IVIG. Thirty-two children (ages: median, 8 years; range, 1.2-17.5 years) with a mean baseline PC of 9.2 × 109/L participated. Eighteen were randomized to regimen A and 14 to regimen B. By 8 hours after initiating therapy, 55% of all children had a PC ≥20 × 109/L (no group difference). By 24 hours, mean PCs were 76.9 × 109/L (B) vs 55 × 109/L (A) (P = .06; P = .035 when adjusted for intergroup differences in patient ages). No patient experienced severe bleeding/unexpected severe AEs. There were statistically fewer IVIG-related headaches in the group receiving combination therapy (P = .046). Our findings show a rapid response to IVIG with/without steroids and provide evidence to support the use of IVMP+IVIG in life-threatening situations. This trial was registered at www.clinicaltrials.gov as #NCT00376077.
Pneumocystis jirovecii pneumonia and institutional prophylaxis practices in CLL patients treated with BTK inhibitors
Authors: Ryan Christine E. , Cheng Matthew P. , Issa Nicolas C. , Brown Jennifer R. , Davids Matthew S.
Published: April 2020

Opportunistic infections (OIs), such as Pneumocystis jirovecii pneumonia (PJP), have been reported in chronic lymphocytic leukemia (CLL) patients treated with ibrutinib, and are an important cause of morbidity and mortality. Currently, there are no international consensus guidelines regarding the use of antimicrobial prophylaxis for OIs, and in particular PJP, in CLL patients treated with Bruton tyrosine kinase inhibitors (BTKi’s). We evaluated the frequency of PJP in CLL patients at our institution who were treated with BTKi’s, and assessed the impact of prophylaxis on reducing the risk of PJP. We identified 217 patients treated with BTKi’s, consisting of 3 cohorts: 143 patients on either BTKi monotherapy with ibrutinib or acalabrutinib, 17 patients receiving ibrutinib combination therapy with umbralisib as part of a clinical trial, and 57 patients receiving ibrutinib in combination with standard chemotherapy, also as part of a clinical trial. Forty-one percent of patients on BTKi monotherapy received prophylaxis, which was given at the discretion of the treating physician. The prevalence of PJP in all patients not on prophylaxis was 3.4% (3 of 87), and, specifically in BTKi-monotherapy patients not on prophylaxis, the PJP prevalence was 2.4% (2 of 85). PJP prophylaxis was effective, as there were no cases of PJP in patients on prophylaxis (0 of 130). The relatively low prevalence of PJP in our study population suggests that routine prophylaxis may not be indicated in CLL patients on BTKi therapy.
Knowledge and associated factors towards cytotoxic drug handling among University of Gondar Comprehensive Specialized Hospital health professionals, institutional-based cross-sectional study
Authors: Simegn Wudneh , Dagnew Baye , Dagne Henok
Published: April 2020

Background

Currently, cancer is among the leading causes of morbidity and mortality in the world. Exposure to CDs may occur during drug preparation and mixing, during drug administration, during transport, and cleaning spills and waste disposal. Healthcare workers who prepare or administer antineoplastic drugs, or who work in areas where these drugs are used, can be exposed to these agents. This also affects the public around the exposed area if appropriate disposal system is not known. Several studies reported increased risks of leukemia and breast cancer among nurses handling CDs and not following safety guidelines. Because of the absence of studies in Ethiopia, the current study was conducted to determine the knowledge level of cytotoxic drug handling and associated factors among health professionals in the University of Gondar Comprehensive Specialized Hospital.

Methods

The institutional-based cross-sectional study was conducted from June to August 2019. Epi info 7.1 was used for data entry and then exported into SPSS version 20 for computing, recording, and statistical analysis. Logistic regression was used to explain the relationship with independent variables.

Results

Four hundred and twelve health professionals participated in the study with 53.4% males. The participants’ mean age was 29.9 (± 5.43) years ranging from 20–60. Two hundred and twenty-three (54.1%) health professionals heard about cytotoxic drugs, and 52.7% (95% UI 47.8–57.8%) had good knowledge of cytotoxic drug handling. Being male sex (AOR = 1.84, 95% CI (1.13–3.00)), age of 29–31 (AOR = 1.99, 95% CI (1.03–3.84)), hearing information about cytotoxic drug handling (AOR = 2.53, 95% CI (1.43–4.47)), ever attended training on cytotoxic drug handling (AOR = 3.15, 95% CI (1.13–8.79)), ever taking courses related to cytotoxic drugs (AOR = 2.03, 95% CI (1.15–3.59)), and good practice (AOR = 3.24, 95% CI (1.95–5.37)) were significantly associated with knowledge towards cytotoxic drug handling. It is therefore imperative to train health professionals and to incorporate CDs handling related course contents while revising curricula to raise the knowledge of health professionals about proper cytotoxic drug handling.

Conclusion

Above half of the study participants scored higher than the median of the cytotoxic drug handling knowledge questions. Sex, age, information about cytotoxic drug handling, training, taking courses related to cytotoxic drugs, and good practice were significantly associated with knowledge towards cytotoxic drugs handling.
Low adherence to exercise may have influenced the proportion of OMERACT-OARSI responders in an integrated osteoarthritis care model: secondary analyses from a cluster-randomised stepped-wedge trial
Authors: Moseng Tuva , Dagfinrud Hanne , van Bodegom-Vos Leti , Dziedzic Krysia , Hagen Kåre Birger , Natvig Bård , Røtterud Jan Harald , Vlieland Thea Vliet , Østerås Nina
Published: April 2020

Background

To address the well-documented gap between hip and knee osteoarthritis (OA) treatment recommendations and current clinical practice, a structured model for integrated OA care was developed and evaluated in a stepped-wedge cluster-randomised controlled trial. The current study used secondary outcomes to evaluate clinically important response to treatment through the Outcome Measures in Rheumatology Clinical Trials clinical responder criteria (OMERACT-OARSI responder criteria) after 3 and 6 months between patients receiving the structured OA care model vs. usual care. Secondly, the study aimed to investigate if the proportion of responders in the intervention group was influenced by adherence to the exercise program inherent in the model.

Methods

The study was conducted in primary healthcare in six Norwegian municipalities. General practitioners and physiotherapists received training in OA treatment recommendations and use of the structured model. The intervention group attended a physiotherapist-led OA education program and performed individually tailored exercises for 8–12 weeks. The control group received usual care. Patient-reported pain, function and global assessment of disease activity during the last week were evaluated using 11-point numeric rating scales (NRS 0–10). These scores were used to calculate the proportion of OMERACT-OARSI responders. Two-level mixed logistic regression models were fitted to investigate differences in responders between the intervention and control group.

Results

Two hundred eighty-four intervention and 109 control group participants with hip and knee OA recruited from primary care in six Norwegian municipalities. In total 47% of the intervention and 35% of the control group participants were responders at 3 or 6 months combined; showing an uncertain between-group difference (ORadjusted 1.38 (95% CI 0.41, 4.67). In the intervention group, 184 participants completed the exercise programme (exercised ≥2 times/week for ≥8 weeks) and 55% of these were classified as responders. In contrast, 28% of the 86 non-completers were classified as responders.

Conclusions

The difference in proportion of OMERACT-OARSI responders at 3 and 6 months between the intervention and control group was uncertain. In the intervention group, a larger proportion of responders were seen among the exercise completers compared to the non-completers.

Clinical trial registration

Clinicaltrials.gov identifier: NCT02333656. Registered 7. January 2015.
Dynamic compression locking system versus multiple cannulated compression screw for the treatment of femoral neck fractures: a comparative study
Authors: Shu Dong-Ping , Xiao Ya-Ping , Bei Ming-Jian , Ji Tao , Peng Yong-Jun , Ma Bing , Li Shao-Gang
Published: April 2020

Background

Femoral neck fractures are one of the problems in clinical treatment. The prognosis is uncertain. Currently, No internal fixation method is superior to other internal fixation methods in the treatment of femoral neck fractures. Therefore, the internal fixation system needs to be further explored. The aim of this study was to compare clinical outcomes of femoral neck dynamic compression locking system (DCLS) and multiple cannulated compression screws(MCCS) in the treatment of femoral neck fractures.

Methods

A prospective analysis of 54 cases of femoral neck fractures treated with either a DCLS (n = 28) or MCCS (n = 26) was conducted between December 2015 and November 2017 in authors’ hospitals. The perioperative and postoperative parameters of the two groups were recorded and evaluated.

Results

Fifty-four patients were followed up for 24–47 months. The etiology was caused by a fall. There was no significant difference in follow-up time, operation time, incision length, surgical blood loss, the incidence of perioperative and postoperative healing complications, and mobility in the two groups (allP > 0.05). The Harris score, fracture healing time, femoral neck shortening, partial weight-bearing time and complete weight-bearing time were significantly better in the DCLS group than in the MCCS group (allP < 0.05). The fracture healing rate in the DCLS group was higher than that in the MCCS group.

Conclusions

The DCLS and MCCS might be equally effective in terms of operation time, incision length, surgical blood loss, the incidence of perioperative and postoperative healing complications, and mobility in the treatment of femoral neck fractures. However, the DCLS is superior to the MCCS in Harris score, fracture healing time, femoral neck shortening, weight-bearing time and fracture healing rate. So, DCLS deserves further study.
Combined lateral peripatellar and posteromedial approaches for Schatzker type IV tibial plateau fractures involving posteromedial plane: a prospective study
Authors: Zhang Jun , Yin Bo , Zhao Jianmin , Li Yihan , Yin Peng , Guo Tao
Published: April 2020

Background

The objective of this study to evaluate prospectively the effectiveness of Schatzker type IV tibial plateau fractures involving posteromedial plane managed by combined lateral peripatellar and posteromedial approaches.

Methods

We analyzed 18 patients with Schatzker type IV tibial plateau fractures involving posteromedial plane. There were 12 males and 6 females with an average of 38.5 years (range, 25–60 years). The mechanism of injury included traffic accident in 15 patients and falling in 3 patients. The injured lower limbs were right in 11 patients and left in 7 patients. The mean time from injury to surgery was 6.78 days (range, 5–9 days). There were 8 patients with meniscus injuries in our study.

Results

The mean operation time was 3.41 h (range, 3–4 h). The mean blood loss was 352.78 ml (range, 300–410 ml). All the injured meniscuses were repaired. All patients were followed up, and the average time of follow up was 16.61 months (range, 14–22 months). Bone union was achieved at a mean of 12 weeks (range, 10–14 weeks). The mean degree of knee extension was 1.11° (range, 0–5°), and the mean degree of knee flexion was 120.56° (range, 110–130°). The mean points of KSS were 83 (range, 74–89 points). According to the criteria of KSS, 14 patients had clinical outcomes rated as excellent and 4 patients were rated as good.

Conclusion

Our results suggested that Combined lateral peripatellar and posteromedial approaches in the treatment of Schatzker type IV tibial plateau fractures involving posteromedial plane acquired satisfying outcomes. It was good for repairing the injured meniscus through our approaches.
Palliative care utilization in oncology and hemato-oncology: a systematic review of cognitive barriers and facilitators from the perspective of healthcare professionals, adult patients, and their families
Authors: Bennardi Marco , Diviani Nicola , Gamondi Claudia , Stüssi Georg , Saletti Piercarlo , Cinesi Ivan , Rubinelli Sara
Published: April 2020

Background

Despite the high potential to improve the quality of life of patients and families, palliative care services face significant obstacles to their use. In countries with high-resource health systems, the nonfinancial and nonstructural obstacles to palliative care services are particularly prominent. These are the cognitive barriers -knowledge and communication barriers- to the use of palliative care. To date no systematic review has given the deserved attention to the cognitive barriers and facilitators to palliative care services utilization.

This study aims to synthesize knowledge on cognitive barriers and facilitators to palliative care use in oncology and hemato-oncology from the experiences of health professionals, patients, and their families.

Methods

A systematic review was conducted. PubMed, PsycINFO, International Association for Hospice and Palliative Care/Cumulative Index of Nursing and Allied Health Literature (IAHPC/CINAHL), and Communication & Mass Media Complete (CMMC) were systematically searched for the main core concepts: palliative care, barriers, facilitators, perspectives, points of view, and related terms and synonyms. After screening of titles, abstracts, and full-texts, 52 studies were included in the qualitative thematic analysis.

Results

Four themes were identified: awareness of palliative care, collaboration and communication in palliative care-related settings, attitudes and beliefs towards palliative care, and emotions involved in disease pathways. The results showed that cognitive barriers and facilitators are involved in the educational, social, emotional, and cultural dimensions of palliative care provision and utilization. In particular, these barriers and facilitators exist both at the healthcare professional level (e.g. a barrier is lack of understanding of palliative care applicability, and a facilitator is strategic visibility of the palliative care team in patient floors and hospital-wide events) and at the patient and families level (e.g. a barrier is having misconceptions about palliative care, and a facilitator is patients’ openness to their own needs).

Conclusions

To optimize palliative care services utilization, awareness of palliative care, and healthcare professionals’ communication and emotion management skills should be enhanced. Additionally, a cultural shift, concerning attitudes and beliefs towards palliative care, should be encouraged.
Mutual interaction between endoplasmic reticulum and mitochondria in nonalcoholic fatty liver disease
Authors: Wang Jin , He Wanping , Tsai Ping-Ju , Chen Pei-Hsuan , Ye Manxiang , Guo Jiao , Su Zhengquan
Published: April 2020

Nonalcoholic fatty liver disease (NAFLD) is a common metabolic syndrome. Imbalances between liver lipid output and input are the direct causes of NAFLD, and hepatic steatosis is the pathological premise and basis for NAFLD progression. Mutual interaction between endoplasmic reticulum stress (ERS) and oxidative stress play important roles in NAFLD pathogenesis. Notably, mitochondria-associated membranes (MAMs) act as a structural bridges for functional clustering of molecules, particularly for Ca2+, lipids, and reactive oxygen species (ROS) exchange. Previous studies have examined the crucial roles of ERS and ROS in NAFLD and have shown that MAM structural and functional integrity determines normal ER- mitochondria communication. Upon disruption of MAM integrity, miscommunication directly or indirectly causes imbalances in Ca2+ homeostasis and increases ERS and oxidative stress. Here, we emphasize the involvement of MAMs in glucose and lipid metabolism, chronic inflammation and insulin resistance in NAFLD and summarize MAM-targeting drugs and compounds, most of which achieve their therapeutic or ameliorative effects on NAFLD by improving MAM integrity. Therefore, targeting MAMs may be a viable strategy for NAFLD treatment. This review provides new ideas and key points for basic NAFLD research and drug development centred on mitochondria and the endoplasmic reticulum.
Orotic acid-treated hepatocellular carcinoma cells resist steatosis by modification of fatty acid metabolism
Authors: Matilainen Johanna , Mustonen Anne-Mari , Rilla Kirsi , Käkelä Reijo , Sihvo Sanna P. , Nieminen Petteri
Published: April 2020

Background

Orotic acid (OA) has been intensively utilized to induce fatty liver in rats. Although the capacity of OA to cause steatosis is species-specific, previous in vitro studies indicate that humans could also be susceptible to OA-induced fatty liver. The aim of the present study was to re-elucidate the potential of OA exposure to modulate the cellular mechanisms involved in both non-alcoholic fatty liver disease pathogenesis and cellular protection from lipid accumulation. In addition, alterations in detailed fatty acid (FA) profiles of cells and culture media were analyzed to assess the significance of lipid metabolism in these phenomena.

Methods

In our experiments, human hepatocellular carcinoma HepG2 cells were exposed to OA. Bacterial endotoxin, lipopolysaccharide (LPS), was used to mimic hepatic inflammation. The lipogenic and inflammatory effects of OA and/or LPS on cells were assessed by labeling cellular lipids with Nile red stain and by performing image quantifications. The expression levels of key enzymes involved in de novo lipogenesis (DNL) and of inflammatory markers related to the disease development were studied by qRT-PCR. FA profiles of cells and culture media were determined from total lipids with gas chromatography–mass spectrometry.

Results

Our data indicate that although OA possibly promotes the first stage of DNL, it does not cause a definite lipogenic transformation in HepG2 cells. Reduced proportions of 16:0, increased stearoyl-Coenzyme A desaturase 1 mRNA expression and relatively high proportions of 16:1n-7 suggest that active delta9-desaturation may limit lipogenesis and the accumulation of toxic 16:0. Inflammatory signaling could be reduced by the increased production of long-chain n-3 polyunsaturated FA (PUFA) and the active incorporation of certain FA, including 18:1n-9, into cells. In addition, increased proportions of 20:4n-6 and 22:6n-3, total PUFA and dimethyl acetal 18:0 suggest that OA exposure may cause increased secretion of lipoproteins and extracellular vesicles.

Conclusions

The present data suggest that, apart from the transcription-level events reported by previous studies, modifications of FA metabolism may also be involved in the prevention of OA-mediated steatosis. Increased delta9-desaturation and secretion of lipoproteins and extracellular vesicles could offer potential mechanisms for further studies to unravel how OA-treated cells alleviate lipidosis.
Association of long-term consumption of repeatedly heated mix vegetable oils in different doses and hepatic toxicity through fat accumulation
Authors: Ambreen Gul , Siddiq Afshan , Hussain Kashif
Published: April 2020

Background

Hepatic diseases are one of the chief reasons for worldwide morbidity and mortality. The increased incidence in Asian countries is driving researchers to explore preventive ways from nature. It is more practical to go with healthy routine edibles like vegetable oils to avoid environmental and chemical hepatic injuries. With the use of thermally oxidized oils overproduction of reactive oxygen species (ROS) with overwhelmed cellular antioxidants defense system results in oxidative stress, the known cause of cardiovascular diseases (CVDs), cancers and neurodegenerative disorders. Little is investigated about the effect of daily used oxidized cooking oils on hepatic function changes with oxidative stress especially in the animal model that mimics the human situation.

Methods

In this study, healthy adult male rabbits of local strain were divided into 4 groups (n = 12). First, two sets of rabbits were treated with 1 and 2 ml/kg/day of repeatedly heated mix vegetable oils (RHMVO) respectively. The third set of rabbits was given 1 ml/kg/day of single time heated mix vegetable oils (STHMVO) and the fourth set of rabbits served as controls and fed with normal rabbit diet to for 16 weeks. Serum liver function markers including total-protein, albumin, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) along with the activity of hepatic antioxidant-enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) for lipid peroxidation were compared among different groups of rabbits. Histopathological examination was performed for all four groups.

Results

Significantly (p < 0.05) elevated hepatic enzymes and MDA levels, with lower total protein, serum albumin, GPx, SOD and CAT levels were found in high and low doses RHMVO treated groups, in comparison to control. In the STHMVO group, all mentioned markers were insignificantly changed. Accumulation of liver fat in low and high dose oil-treated groups was further confirmed under the microscopic examination of liver tissues, presented significant fat accumulation in liver tissues, in addition, 40–60% increased oxidative stress compared to control, in a dose-dependent manner.

Conclusions

These results conclude that consumption of thermally oxidized mix vegetable oils for longer duration can impair the liver function and destroy its histological structure significantly through fat accumulation and oxidative stress both in high as well as low doses.
Mid-term effect of balloon aortic valvuloplasty on mitral regurgitation in aortic stenosis
Authors: Masaki Ryota , Iwasaki Masamichi , Tanaka Hidekazu , Hamana Tomoyo , Odajima Susumu , Fujimoto Wataru , Kuroda Koji , Hatani Yutaka , Inoue Takumi , Okamoto Hiroshi , Okuda Masanori , Hayashi Takatoshi , Hirata Ken-ichi
Published: April 2020

Background

Balloon aortic valvuloplasty (BAV) offers an alternative to conventional aortic valve replacement in elderly and frail patients with severe aortic stenosis (AS) for whom there are no other effective options. We aimed to investigate the mid-term effect of BAV on mitral regurgitation (MR) in patients with severe AS.

Methods

Our analysis was based on the data from 83 patients with severe AS (mean age, 86 ± 5 years; female, 68) treated using BAV. Echocardiography was performed before the procedure and at 1 and 3 months after. MR was quantified by measuring the MR jet area, with more-than-moderate MR being clinically significant.

Results

Forty patients were classified in this group (MR group). Significant reduction of MR was observed in the MR group at 1 month and 3 months after procedure, with no improvement in patients in the non-MR group. At 3 months, 15 of the 40 patients in the MR group still had significant MR, with the change at 1 month in the left ventricular end-systolic dimension (OR: 1.36; 95% CI: 1.05–1.76; P = 0.022) and MR jet area (OR: 1.95; 95% CI: 1.16–3.29; P = 0.012) being predictive of persisting significant MR at 3 months after BAV. The prevalence of New York Heart Association functional class III or IV decreased at 1 and 3 months after BAV in both groups.

Conclusions

BAV provides a useful therapeutic strategy for elderly patients with severe AS who are not candidates for surgical or transcatheter aortic valve replacement, especially in those with significant MR.
Linear-time algorithms for phylogenetic tree completion under Robinson–Foulds distance
Authors: Bansal Mukul S.
Published: April 2020

Background

We consider two fundamental computational problems that arise when comparing phylogenetic trees, rooted or unrooted, with non-identical leaf sets. The first problem arises when comparing two trees where the leaf set of one tree is a proper subset of the other. The second problem arises when the two trees to be compared have only partially overlapping leaf sets. The traditional approach to handling these problems is to first restrict the two trees to their common leaf set. An alternative approach that has shown promise is to first complete the trees by adding missing leaves, so that the resulting trees have identical leaf sets. This requires the computation of an optimal completion that minimizes the distance between the two resulting trees over all possible completions.

Results

We provide optimal linear-time algorithms for both completion problems under the widely-used Robinson–Foulds (RF) distance measure. Our algorithm for the first problem improves the time complexity of the current fastest algorithm from quadratic (in the size of the two trees) to linear. No algorithms have yet been proposed for the more general second problem where both trees have missing leaves. We advance the study of this general problem by proposing a useful restricted version of the general problem and providing optimal linear-time algorithms for the restricted version. Our experimental results on biological data sets suggest that completion-based RF distances can be very different compared to traditional RF distances.
Effects of adding sodium dichloroacetate to low-protein diets on nitrogen balance and amino acid metabolism in the portal-drained viscera and liver of pigs
Authors: Sun Weizhong , Li Yunxia , Tang Zhiru , Chen Huiyuan , Wan Ke , An Rui , Wu Liuting , Sun Zhihong
Published: April 2020

Background

Identifying regulatory measures to promote glucose oxidative metabolism while simultaneously reducing amino acid oxidative metabolism is one of the foremost challenges in formulating low-protein (LP) diets designed to reduce the excretion of nitrogen-containing substances known to be potential pollutants. In this study, we investigated the effects of adding sodium dichloroacetate (DCA) to a LP diet on nitrogen balance and amino acid metabolism in the portal-drained viscera (PDV) and liver of pigs.

To measure nitrogen balance, 18 barrows (40 ± 1.0 kg) were fed one of three diets (n = 6 per group): 18% crude protein (CP, control), 13.5% CP (LP), and 13.5% CP + 100 mg DCA/kg dry matter (LP-DCA). To measure amino acid metabolism in the PDV and liver, 15 barrows (40 ± 1.0 kg) were randomly assigned to one of the three diets (n = 5 per group). Four essential amino acids (Lys, Met, Thr, and Trp) were added to the LP diets such that these had amino acid levels comparable to those of the control diet.

Results

The LP-DCA diet reduced nitrogen excretion in pigs relative to that of pigs fed the control diet (P < 0.05), without any negative effects on nitrogen retention (P > 0.05). There were no differences between the control and LP-DCA groups with respect to amino acid supply to the liver and extra-hepatic tissues in pigs (P > 0.05). The net release of ammonia into the portal vein and production rate of urea in the liver of pigs fed the LP-DCA diet was reduced relative to that of pigs fed the control and LP diets (P < 0.05).

Conclusion

The results indicated that addition of DCA to a LP diet can efficiently reduce nitrogen excretion in pigs and maximize the supply of amino acids to the liver and extra-hepatic tissues.
Reduced integration schemes in micromorphic computational homogenization of elastomeric mechanical metamaterials
Authors: Rokoš Ondřej , Zeman Jan , Doškář Martin , Krysl Petr
Published: April 2020

Exotic behaviour of mechanical metamaterials often relies on an internal transformation of the underlying microstructure triggered by its local instabilities, rearrangements, and rotations. Depending on the presence and magnitude of such a transformation, effective properties of a metamaterial may change significantly. To capture this phenomenon accurately and efficiently, homogenization schemes are required that reflect microstructural as well as macro-structural instabilities, large deformations, and non-local effects. To this end, a micromorphic computational homogenization scheme has recently been developed, which employs the particular microstructural transformation as a non-local mechanism, magnitude of which is governed by an additional coupled partial differential equation. Upon discretizing the resulting problem it turns out that the macroscopic stiffness matrix requires integration of macro-element basis functions as well as their derivatives, thus calling for higher-order integration rules. Because evaluation of a constitutive law in multiscale schemes involves an expensive solution of a non-linear boundary value problem, computational efficiency of the micromorphic scheme can be improved by reducing the number of integration points. Therefore, the goal of this paper is to investigate reduced-order schemes in computational homogenization, with emphasis on the stability of the resulting elements. In particular, arguments for lowering the order of integration from expensive mass-matrix to a cheaper stiffness-matrix equivalent are outlined first. An efficient one-point integration quadrilateral element is then introduced and a proper hourglass stabilization is discussed. Performance of the resulting set of elements is finally tested on a benchmark bending example, showing that we achieve accuracy comparable to the full quadrature rules, whereas computational cost decreases proportionally to the reduction in the number of quadrature points used.
The benefits and caveats of using clickstream data to understand student self-regulatory behaviors: opening the black box of learning processes
Authors: Baker Rachel , Xu Di , Park Jihyun , Yu Renzhe , Li Qiujie , Cung Bianca , Fischer Christian , Rodriguez Fernando , Warschauer Mark , Smyth Padhraic
Published: April 2020

Student clickstream data—time-stamped records of click events in online courses—can provide fine-grained information about student learning. Such data enable researchers and instructors to collect information at scale about how each student navigates through and interacts with online education resources, potentially enabling objective and rich insight into the learning experience beyond self-reports and intermittent assessments. Yet, analyses of these data often require advanced analytic techniques, as they only provide a partial and noisy record of students’ actions. Consequently, these data are not always accessible or useful for course instructors and administrators. In this paper, we provide an overview of the use of clickstream data to define and identify behavioral patterns that are related to student learning outcomes. Through discussions of four studies, we provide examples of the complexities and particular considerations of using these data to examine student self-regulated learning.
Physician Practice Variability in the Use of Extended-Fraction Radiation Therapy for Bone Metastases: Are We Choosing Wisely?
Authors: Gupta Arjun , Wang Peiqi , Sedhom Ramy , Chino Fumiko , Waddle Mark R. , Miller Robert C. , Johnson David H. , Sanford Nina N. , Narang Amol , Alcorn Sara R. , Makary Martin A.
Published: April 2020

PURPOSE:

Routine use of extended-fraction (> 10 fractions) radiation therapy (RT) for palliation of bone metastases is recognized as a low-value intervention by the American Society for Radiation Oncology. We examined contemporary practice patterns of, and physician characteristics associated with extended-fraction RT use.

MATERIALS AND METHODS:

We conducted a retrospective cohort study using Medicare fee-for-service data. We included patients who underwent 2- or 3-dimensional external-beam RT for bone metastases between January 1, 2016, and December 31, 2018. Physicians treating > 10 patients over the study period were analyzed for their individual practice. Hierarchic logistic regression modeling was used to identify patient- and physician-level factors associated with extended-fraction RT use.

RESULTS:

A total of 12,221 patients (median age, 75.6 years; 40.9% women, 87.6% white) were included. The rate of extended-fraction RT was 23.4%. A total of 1,432 physicians treated any patient. Among the 382 physicians treating > 10 patients, 127 (33.2%) used extended-fraction RT > 30% (consensus threshold). Physician factors associated with decreased odds of extended-fraction RT were years since medical school graduation (≤ 10 years and 11-20 years v ≥ 31 years: adjusted odds ratio [aOR], 0.32 [95% CI, 0.20 to 0.51] and 0.64 [95% CI, 0.44 to 0.93]) and practicing in the Northeast or Midwest versus the South (aOR, 0.36 [95% CI, 0.22 to 0.58] and 0.48 [95% CI, 0.31 to 0.74]). Physicians treating > 20 patients ( v 11-14 patients) over the study period had increased odds of delivering extended-fraction RT (aOR, 1.53 [95% CI, 1.10 to 2.12]).

CONCLUSION:

In this study, almost one fourth of patients received extended-fraction RT, and one third of physicians had an extended-fraction RT use rate of > 30%. Personalized feedback of performance data, clinical pathways and peer review, and updated reimbursement models are potential mechanisms to address this low-value care.
Evidence in Support for the Progressive Nature of Ovarian Endometriomas
Authors: Ding Ding , Wang Xi , Chen Yishan , Benagiano Giuseppe , Liu Xishi , Guo Sun-Wei
Published: April 2020

Context

Whether endometriosis is a progressive disease is a highly contentious issue. While progression is reported to be unlikely in asymptomatic deep endometriosis, progression in symptomatic deep endometriosis has recently been reported, especially in menstruating women. However, pathophysiological reasons for these differences are unclear.

Objective

This study was designed to investigate whether ovarian endometrioma (OE) is progressive or not.

Setting, Design, Patients, Intervention and Main Outcome Measures

Thirty adolescent patients, aged 15 to 19 years, and 32 adult patients, aged 35 to 39 years, all laparoscopically and histologically diagnosed with OE, were recruited into this study after informed consent. Their demographic and clinical information were collected. Their OE tissue samples were collected and subjected to immunohistochemical analysis for E-cadherin, α-smooth muscle actin (α-SMA), desmin, and adrenergic receptor β2 (ADRB2), as well as quantification of lesional fibrosis by Masson trichrome staining.

Results

OE lesions from the adolescent and adult patients are markedly different, with the latter exhibiting more extensive and thorough progression and more extensive fibrosis, suggesting that lesions in adults progressed to a more advanced stage. Adult lesions and higher staining level of α-SMA and ADRB2 are positively associated with the extent of lesional fibrosis, while the lesion size and the E-cadherin staining are negatively associated.

Conclusions

Our data provide a more definitive piece of evidence suggesting that OE is a progressive disease, since the adult lesions have had a longer time to progress. In addition, the pace of progression depends on lesional age as well as the severity of endometriosis-associated dysmenorrhea, if any.
An Activating Deletion Variant in the Submembrane Region of Natriuretic Peptide Receptor-B Causes Tall Stature
Authors: Lauffer Peter , Miranda-Laferte Erick , van Duyvenvoorde Hermine A , van Haeringen Arie , Werner Franziska , Boudin Eveline , Schmidt Hannes , Mueller Thomas D , Kuhn Michaela , van der Kaay Daniëlle C M
Published: April 2020

Context

C-type natriuretic peptide (CNP) is critically involved in endochondral bone growth. Variants in the genes encoding CNP or its cyclic guanosine monophosphate (cGMP)-forming receptor (natriuretic peptide receptor-B [NPR-B], gene NPR2) cause monogenic growth disorders. Here we describe a novel gain-of-function variant of NPR-B associated with tall stature and macrodactyly of the great toes (epiphyseal chondrodysplasia, Miura type).

Design

History and clinical characteristics of 3 family members were collected. NPR2 was selected for sequencing. Skin fibroblasts and transfected HEK-293 cells were used to compare mutant versus wild-type NPR-B activities. Homology modeling was applied to understand the molecular consequences of the variant.

Results

Mother’s height was +2.77 standard deviation scores (SDS). The heights of her 2 daughters were +1.96 SDS at 7 years and +1.30 SDS at 4 years of age. Skeletal surveys showed macrodactyly of the great toes and pseudo-epiphyses of the mid- and proximal phalanges. Sequencing identified a novel heterozygous variant c.1444_1449delATGCTG in exon 8 of NPR2, predicted to result in deletion of 2 amino acids Met482-Leu483 within the submembrane region of NPR-B. In proband’s skin fibroblasts, basal cGMP levels and CNP-stimulated cGMP production were markedly increased compared with controls. Consistently, assays with transfected HEK-293 cells showed markedly augmented baseline and ligand-dependent activity of mutant NPR-B.

Conclusions

We report the second activating variant within the intracellular submembrane region of NPR-B resulting in tall stature and macrodactyly. Our functional and modeling studies suggest that this domain plays a critical role in the baseline conformation and ligand-dependent structural rearrangement of NPR-B required for cGMP production.
Effect of Dural Puncture Epidural Technique Combined With Programmed Intermittent Epidural Bolus on Labor Analgesia Onset and Maintenance: A Randomized Controlled Trial
Authors: Song Yujie , Du Weijia , Zhou Shuangqiong , Zhou Yao , Yu Yibing , Xu Zhendong , Liu Zhiqiang
Published: April 2020

BACKGROUND:

The dural puncture epidural (DPE) technique is associated with faster onset than the conventional epidural (EP) technique for labor analgesia. The programmed intermittent epidural bolus (PIEB) mode for maintaining labor analgesia allows for lower anesthetic drug consumption than the continuous epidural infusion (CEI) mode. Whether DPE technique with PIEB mode offers additional benefits for analgesia onset, local anesthetic drug consumption, and side effects versus EP or DPE techniques with CEI mode remains unclear.

METHODS:

Nulliparous women with a visual analog scale (VAS) pain score >50 mm and cervical dilation <5 cm were randomly assigned to receive EP + CEI, DPE + CEI, or DPE + PIEB for labor analgesia. A 25-gauge needle was used for dural puncture. Analgesia was initiated with 10 mL of 0.1% ropivacaine with 0.3 µg/mL of sufentanil and maintained with the same solution at 8 mL/h in all groups. A 5-mL patient-controlled epidural analgesia (PCEA) bolus was programmed with a 20-minute lockout. Breakthrough pain not amendable by PCEA was treated with provider boluses of 5 mL of 0.125% ropivacaine. The primary outcome was “time to adequate analgesia,” defined as a VAS pain score ≤30 mm during 2 consecutive contractions, and was analyzed using Kaplan–Meier curves and a Cox proportional hazard model. Secondary outcomes included the VAS scores, ropivacaine consumption, sensory block level to ice, PCEA and provider boluses intervention, mode of delivery, duration of labor, Bromage scores, Apgar scores, occurrence of side effects, and maternal satisfaction with the anesthesia.

RESULTS:

A total of 116 women were included (38 in the EP + CEI group, 40 in the DPE + CEI group, and 38 in the DPE + PIEB group). Adequate anesthesia was achieved faster in the DPE + CEI and DPE + PIEB groups than in the EP + CEI group (hazard ratio = 1.705; 95% confidence interval [CI], 1.039–2.800; P = .015; and hazard ratio = 1.774; 95% CI, 1.070–2.941; P = .012, respectively). DPE technique with PIEB mode was associated with the fewest PCEA boluses and the lowest hourly ropivacaine consumption (both P < .001). There were no differences in the duration of labor, mode of delivery, Bromage scores, newborn Apgar scores, incidence of side effects, and maternal satisfaction scores among the groups.

CONCLUSIONS:

The use of DPE technique for neuraxial analgesia was associated with faster onset than the use of the EP technique. DPE technique with PIEB mode achieved the greatest drug-sparing effect without increasing maternal or neonatal side effects.