bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers to and competency with the use of metered dose inhaler and its impact on disease control among adult asthmatic patients in Ethiopia
Authors: Abegaz Tadesse Melaku , Shegena Efrata Ashuro , Gessie Natnael Fentie , Gebreyohannes Eyob Alemayehu , Seid Mohammed Assen
Published: February 2020

Background

Asthma is one of the chronic diseases which affects the airway, and inhalers are the preferred medications to treat this problem. Improper inhalational technique leads to decreased efficacy of the medication by reducing its deposition in the lungs. The aim of this study was to assess the barriers to and competency with the use of Metered Dose Inhaler (MDI) and its impact on disease control among adult asthmatic patients.

Methods

A prospective cross-sectional study was conducted in University of Gondar comprehensive specialized hospital outpatient department (OPD) chronic follow up from 12-March-2018 to 15-May- 2018. Patients were interviewed face to face with questions which determined their competency, asthma control level and barriers for inhaler use.

Result

Overall, 307 asthmatic patients were included in the study. More than half of participants were females, 170 (55.4%) and lived in urban area 185 (60.3%). The mean age of the respondents was 51.77 years with a standard deviation of ±15.40. The cost of medication, 282 (91.9%) and the perception that medication should be used in response to symptoms but not on a regular basis 277 (90.2%) were the most identified barriers. Only 56 (18.2%) were competent for Metered Dose Inhaler use (MDIU) and 17 (5.5%) patients had well controlled asthma. Being not competent AOR 0.168[0.41–0.687] was one of the factors decreasing asthma control.

Conclusion

Generally from this study, cost of the medication and the perception that medication should be used only for symptoms were the major identified barriers that affect the MDI use among asthmatic patients. Patients show very poor competence to their MDI which in turn led to poor asthma control. So, patients need to be taught the correct inhaler technique in the hospital and pharmacy while they came for follow up every time.
Noise after total knee arthroplasty has limited effect on joint awareness and patient-reported clinical outcomes: retrospective study
Authors: Taniguchi Hiroto , Itoh Masafumi , Yoshimoto Nobuyuki , Itou Junya , Kuwashima Umito , Okazaki Ken
Published: February 2020

Background

Some patients complain of noise after total knee arthroplasty (TKA). Controversy still exists on how the noise affects the clinical outcomes, including joint awareness, after TKA. The Forgotten Joint Score—12 (FJS-12) measures the clinical outcomes focusing on joint awareness after surgery. The Knee Society Scoring System—2011 (KSS-2011) includes questionnaires for satisfaction, expectation, and functional activities. The aim of this study is to clarify the relationship among FJS-12, KSS-2011, and the noise. Furthermore, the relationship between FJS-12 and KSS-2011 was validated.

Methods

Using FJS-12 and KSS-2011, 295 knees from 225 patients who underwent TKA were retrospectively evaluated. Noise perception was evaluated by a questionnaire with five grades, a method that follows the questionnaire form of FJS-12 (“Are you aware of the noise of your artificial joint?”; never, almost never, seldom, sometimes, mostly). Correlations among FJS-12, KSS-2011, and noise were analyzed. The patients were divided into four groups based on the mechanism of their implant [cruciate retaining, posterior stabilized, cruciate sacrificed, and bicruciate stabilized (BCS)]. FJS-12, KSS-2011, and noise were compared among the groups.

Results

A strong correlation was found between FJS-12 and total score of KSS-2011 (0.70; P < 0.001). FJS-12 correlated with KSS-2011 subcategories of “symptoms,” “satisfaction,” and “standard activities,” with correlation coefficients at approximately 0.60. Noise had weak correlations with FJS-12 (0.28; P < 0.001) and KSS-2011 (0.20 P < 0.001). In comparing the TKA mechanisms, BCS had remarkably better KSS-2011 and greater movement range but worse noise scores.

Conclusions

Noise perception after TKA had limited effect on joint awareness and clinical outcomes. FJS-12 correlated strongly with KSS-2011 and associated with satisfaction, residual symptoms, and daily activities, as assessed by KSS-2011 subscores.

Trial registration

This study was approved by the Medical Ethical Committee of the Tokyo Women’s Medical University (approval number: 4681 on March 2, 2018).
Correction to: Cross-sectional study of associations between normal body weight with central obesity and hyperuricemia in Japan
Authors: Shirasawa Takako , Ochiai Hirotaka , Yoshimoto Takahiko , Nagahama Satsue , Watanabe Akihiro , Yoshida Reika , Kokaze Akatsuki
Published: February 2020

After publication of this article [1], it was brought to our attention that there is an error in the Table 5, which “Cases” should be revised to “HU” in Table 5. The original publication has been corrected.
The influence of spirituality on decision-making in palliative care outpatients: a cross-sectional study
Authors: Rego Francisca , Gonçalves Florbela , Moutinho Susana , Castro Luísa , Nunes Rui
Published: February 2020

Background

Decision-making in palliative care can be complex due to the uncertain prognosis and general fear surrounding decisions. Decision-making in palliative care may be influenced by spiritual and cultural beliefs or values. Determinants of the decision-making process are not completely understood, and spirituality is essential for coping with illness. Thus, this study aims to explore the influence of spirituality on the perception of healthcare decision-making in palliative care outpatients.

Methods

A cross-sectional study was developed. A battery of tests was administered to 95 palliative outpatients, namely: sociodemographic questionnaire (SQ), Decisional Conflict Scale (DCS), Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being scale (FACIT-Sp), and a semi-structured interview (SSI) to study one’s perception of spirituality and autonomy in decision-making. Statistical analyses involved descriptive statistics for SQ and SSI. The Mann-Whitney test was used to compare scale scores between groups and correlations were used for all scales and subscales. The analysis of patients’ definitions of spirituality was based on the interpretative phenomenological process.

Results

Spiritual wellbeing significantly correlated with greater levels of physical, emotional and functional wellbeing and a better quality of life. Greater spiritual wellbeing was associated with less decisional conflict, decreased uncertainty, a feeling of being more informed and supported and greater satisfaction with one’s decision. Most patients successfully implemented their decision and identified themselves as capable of early decision-making. Patients who were able to implement their decision presented lower decisional conflict and higher levels of spiritual wellbeing and quality of life. Within the 16 themes identified, spirituality was mostly described through family. Patients who had received spiritual care displayed better scores of spiritual wellbeing, quality of life and exhibited less decisional conflict. Patients considered spirituality during illness important and believed that the need to receive spiritual support and specialised care could enable decision-making when taking into consideration ones’ values and beliefs.

Conclusion

The impact of spiritual wellbeing on decision-making is evident. Spirituality is a key component of overall wellbeing and it assumes multidimensional and unique functions. Individualised care that promotes engagement in decision-making and considers patients’ spiritual needs is essential for promoting patient empowerment, autonomy and dignity.
A combination of 3-D discrete wavelet transform and 3-D local binary pattern for classification of mild cognitive impairment
Authors:   For Alzheimer’s Disease Neuroimaging Initiative, Bhasin Harsh , Agrawal Ramesh Kumar
Published: February 2020

Background

The detection of Alzheimer’s Disease (AD) in its formative stages, especially in Mild Cognitive Impairments (MCI), has the potential of helping the clinicians in understanding the condition. The literature review shows that the classification of MCI-converts and MCI-non-converts has not been explored profusely and the maximum classification accuracy reported is rather low. Thus, this paper proposes a Machine Learning approach for classifying patients of MCI into two groups one who converted to AD and the others who are not diagnosed with any signs of AD. The proposed algorithm is also used to distinguish MCI patients from controls (CN). This work uses the Structural Magnetic Resonance Imaging data.

Methods

This work proposes a 3-D variant of Local Binary Pattern (LBP), called LBP-20 for extracting features. The method has been compared with 3D-Discrete Wavelet Transform (3D-DWT). Subsequently, a combination of 3D-DWT and LBP-20 has been used for extracting features. The relevant features are selected using the Fisher Discriminant Ratio (FDR) and finally the classification has been carried out using the Support Vector Machine.

Results

The combination of 3D-DWT with LBP-20 results in a maximum accuracy of 88.77. Similarly, the proposed combination of methods is also applied to distinguish MCI from CN. The proposed method results in the classification accuracy of 90.31 in this data.

Conclusion

The proposed combination is able to extract relevant distribution of microstructures from each component, obtained with the use of DWT and thereby improving the classification accuracy. Moreover, the number of features used for classification is significantly less as compared to those obtained by 3D-DWT. The performance of the proposed method is measured in terms of accuracy, specificity and sensitivity and is found superior in comparison to the existing methods. Thus, the proposed method may contribute to effective diagnosis of MCI and may prove advantageous in clinical settings.
Defining patient communication needs during hospitalization to improve patient experience and health literacy
Authors: Marca-Frances Guillem , Frigola-Reig Joan , Menéndez-Signorini Jesica A. , Compte-Pujol Marc , Massana-Morera Eulàlia
Published: February 2020

Background

In order to play an active role in their health care, patients need information and motivation. Current delivery systems limit patients’ involvement because they do not routinely provide them with enough details of their own clinical results, conditions and other important clinical data. The purpose of this study was to identify, from the perspective of patients, which topics matter the most, who should be communicating them, and when and how should they be provided.

Methods

We conducted a qualitative, phenomenological study analysing the content of subjective experiences, feelings and behaviours. We organized two focus groups with 13 participants and 15 in-depth interviews. Transcripts of the focus groups and interviews were checked for accuracy and then entered into Atlas ti™ v7.5.13 qualitative software. Two independent researchers performed a qualitative inductive content analysis to classify the data in two levels: themes and categories.

Results

The qualitative analysis provided 377 units of meaning synthesized into 22 categories and six themes: hospitalization procedure, Health Literacy relating to the patient’s condition, information content, satisfaction, professional-patient relationship, and patient proactivity. Patients described which information they wished for, when they needed it, and who would provide it, usually related to actions such as admission, discharge or diagnostic tests. Oral information was more difficult to comprehend than the written kind, as patients can check written information several times if needed. Nurses were the most available professionals, and patients found easier to relate to them and ask them questions. Moreover, patients identified physicians as those professionals responsible for providing clinical information.

Conclusions

Our results showed that patients suffered from poor Health Literacy regarding their personal condition, as they were unable to describe the symptoms, the type of tests being performed or their results, and some of them also had difficulties in naming the specific disease or comorbidities they had. During the hospitalization process, patients were in good shape to come with doubts and actively asked for more information. Healthcare organizations and professionals were offered the chance to ensure the correct communication and comprehension to their patients.
The atherogenic index of plasma plays an important role in predicting the prognosis of type 2 diabetic subjects undergoing percutaneous coronary intervention: results from an observational cohort study in China
Authors: Qin Zheng , Zhou Kuo , Li Yueping , Cheng Wanjun , Wang Zhijian , Wang Jianlong , Gao Fei , Yang Lixia , Xu Yingkai , Wu Yafeng , He Hua , Zhou Yujie
Published: February 2020

Background

Many studies have reported the predictive value of the atherogenic index of plasma (AIP) in the progression of atherosclerosis and the prognosis of percutaneous coronary intervention (PCI). However, the utility of the AIP for prediction is unknown after PCI among type 2 diabetes mellitus (T2DM).

Methods

2356 patients with T2DM who underwent PCI were enrolled and followed up for 4 years. The primary outcome was major cardiovascular and cerebrovascular adverse events (MACCEs), considered to be a combination of cardiogenic death, myocardial infarction, repeated revascularization, and stroke. Secondary endpoints included all-cause mortality, target vessel revascularization (TVR), and non-target vessel revascularization (non-TVR). Multivariate Cox proportional hazards regression modelling found that the AIP was correlated with prognosis and verified by multiple models. According to the optimal cut-off point of the ROC curve, the population was divided into high/low-AIP groups. A total of 821 pairs were successfully matched using propensity score matching. Then, survival analysis was performed on both groups.

Results

The overall incidence of MACCEs was 20.50% during a median of 47.50 months of follow-up. The multivariate Cox proportional hazards regression analysis before matching suggested that the AIP was an independent risk factor for the prognosis of T2DM after PCI (hazard ratio [HR] 1.528, 95% CI 1.100–2.123, P = 0.011). According to the survival analysis of the matched population, the prognosis of the high AIP group was significantly worse than that of the low AIP group (HR (95% CI) 1.614 (1.303–2.001), P < 0.001), and the difference was mainly caused by repeat revascularization. The low-density lipoprotein-cholesterol (LDL-C) level did not affect the prognosis of patients with T2DM (P = 0.169), and the effect of the AIP on prognosis was also not affected by LDL-C level (P < 0.001).

Conclusions

The AIP, a comprehensive index of lipid management in patients with T2DM, affects prognosis after PCI. The prognosis of diabetic patients with high levels of the AIP included more MACCEs and was not affected by LDL-C levels. It is recommended to monitor the AIP for lipid management in diabetic patients after PCI and ensure that the AIP is not higher than 0.318.

Trial registrationThis is an observational cohort study that does not involve interventions. So we didn’t register. We guarantee that the research is authentic and reliable, and hope that your journal can give us a chance.
Variations in the estimated intake of acrylamide from food in the Japanese population
Authors: Kito Kumiko , Ishihara Junko , Yamamoto Junpei , Hosoda Takayuki , Kotemori Ayaka , Takachi Ribeka , Nakamura Kazutoshi , Tanaka Junta , Yamaji Taiki , Shimazu Taichi , Ishii Yuri , Sawada Norie , Iwasaki Motoki , Iso Hiroyasu , Sobue Tomotaka , Tsugane Shoichiro
Published: February 2020

Background

Due to concerns of carcinogenicity, it is necessary to assess long-term acrylamide exposure in individuals. Whether the available methods of estimating acrylamide intake can indicate long-term exposure remains unknown. We examined variations in the estimated dietary acrylamide intake of the Japanese population.

Methods

The study included 240 participants aged 40–74 years who were a part of the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT). Twelve-day dietary records (DRs) were collected over a one-year period, and food frequency questionnaires (FFQs) were collected twice during the year. Dietary acrylamide intake was estimated from an acrylamide content database. Within-individual variations and between-individual variations were calculated using the random effects model. A linear regression analysis was performed to identify foods with large between-individual variations.

Results

The ratios of within-individual variance to between-individual variation were 3.2 for men and 4.3 for women. Days of DRs required to estimate the usual individual intake within 20% of the true mean intake with 95% confidence were 60 days for men and 66 days for women. Coffee/cocoa, potato, and green tea contributed to between-individual variations, in that order, and seven foods contributed to 93% of the between-individual variation.

Conclusions

Estimating the acrylamide intake using DRs requires an extended data collection period to estimate the intragroup ranking and habitual intake of individuals. Long-term exposure assessments should be based on methods with less potential for measurement errors, such as the use of biomarkers.
Biomechanical effect of a lateral hinge fracture for a medial opening wedge high tibial osteotomy: finite element study
Authors: Kang Kyoung-Tak , Koh Yong-Gon , Lee Jin-Ah , Lee Jae Jung , Kwon Sae Kwang
Published: February 2020

Background

This study aimed to investigate the biomechanical effect on the Takeuchi classification of lateral hinge fracture (LHF) after an opening wedge high tibial osteotomy (HTO).

Methods

We performed an FE simulation for type I, type II, and type III in accordance with the Takeuchi classification. The stresses on the bone and plate, wedge micromotion, and forces on ligaments were evaluated to investigate stress-shielding effect, plate stability, and biomechanical change, respectively, in three different types of LHF HTO and with the HTO without LHF model (non-LHF) models.

Results

The greatest stress-shielding effect and wedge micromotion were observed in type II LHF (distal portion fracture). The type II and type III (lateral plateau fracture) models exhibited a reduction in PCL force and an increase in ACL force compared with the HTO without LHF model. However, the type I (osteotomy line fracture) and HTO without LHF models did not exhibit a significant biomechanical effect. This study demonstrates that Takeuchi type II and type III LHF models provide unstable structures compared with the type I and HTO without LHF models.

Conclusions

HTO should be performed while considering a medial opening wedge HTO to avoid a type II and type III LHF as a potential complication.
Immunoproteomic and mass spectrometric analysis of Eimeria acervulina antigens recognized by antisera from chickens infected with E. acervulina, E. tenella or E. necatrix
Authors: Liu Jin , Tuo Wenbin , Wu Xiangdong , Xiong Jiaming , Yu Enchao , Yin Chao , Ma Zhiwu , Liu Liheng
Published: February 2020

Background

Coccidiosis is caused byEimeriaspp. and can result in severe economic losses to the global poultry industry. Due to anticoccidial drug resistance rapidly developing in the parasites and drug residues in poultry products, efficacious and safe alternative coccidia control measures are needed. The objective of the present study was to identify common protective antigens which may be used as vaccine candidates in the development of subunit, multivalent, cross-protective vaccines against most of the economically importantEimeriaspecies.

Methods

Whole sporozoite proteins ofEimeria acervulinawere prepared and analyzed by 2-dimensional gel electrophoresis (2-DE) followed by western blotting using immune sera specific toE. tenella,E. acervulina, orE. necatrix. The protein spots detected by all three immune sera were then excised from the preparative gel and protein ID was performed by MALDI-TOF-MS/MS.

Results

Approximately 620E. acervulinasporozoite protein spots were demonstrated by 2-DE with silver staining, among which 23 protein spots were recognized by immune sera specific to all threeEimeriaspecies. The results showed that 21 putativeE. acervulinaproteins were identified, which include proteins with known enzymatic properties, and those which are involved in protein translation, transport and trafficking, and ribosomal biogenesis and functions. There is one protein which may be involved in transcription and one heat-shock protein. Two proteins contain predicted domains, but with no apparent functions known. There were 2 protein spots which had no detectable proteins. None of the proteins has a predicted signal peptide or a transmembrane domain; however, 6 of the 21 putative proteins were predicted to be potentially secretory through the non-classical pathway.

Conclusions

Our study identified a diverse group of antigens immunologically common to all threeEimeriaspecies, none of which was previously characterized and tested as a vaccine candidate. Further research on immunogenicity and cross-protective potential of these individual proteins as vaccine candidates will aid the development of vaccines against the most common and pathogenicEimeriaspp.
Can rumen bacteria communicate to each other?
Authors: Won Mi-Young , Oyama Linda B. , Courtney Stephen J. , Creevey Christopher J. , Huws Sharon A.
Published: February 2020

Background

The rumen contains a myriad of microbes whose primary role is to degrade and ferment dietary nutrients, which then provide the host with energy and nutrients. Rumen microbes commonly attach to ingested plant materials and form biofilms for effective plant degradation. Quorum sensing (QS) is a well-recognised form of bacterial communication in most biofilm communities, with homoserine lactone (AHL)-based QS commonly being used by Gram-negative bacteria alone and AI-2 Lux-based QS communication being used to communicate across Gram-negative and Gram-positive bacteria. However, bacterial cell to cell communication in the rumen is poorly understood. In this study, rumen bacterial genomes from the Hungate collection and Genbank were prospected for QS-related genes. To check that the discovered QS genes are actually expressed in the rumen, we investigated expression levels in rumen metatranscriptome datasets.

Results

A total of 448 rumen bacterial genomes from the Hungate collection and Genbank, comprised of 311 Gram-positive, 136 Gram-negative and 1 Gram stain variable bacterium, were analysed. Abundance and distribution of AHL and AI-2 signalling genes showed that only one species (Citrobacter sp. NLAE-zl-C269) of a Gram-negative bacteria appeared to possess an AHL synthase gene, while the Lux-based genes (AI-2 QS) were identified in both Gram-positive and Gram-positive bacteria (191 genomes representing 38.2% of total genomes). Of these 192 genomes, 139 are from Gram-positive bactreetteria and 53 from Gram-negative bacteria. We also found that the genera Butyrivibrio, Prevotella, Ruminococcus and Pseudobutyrivibrio, which are well known as the most abundant bacterial genera in the rumen, possessed the most lux-based AI-2 QS genes. Gene expression levels within the metatranscriptome dataset showed that Prevotella, in particular, expressed high levels of LuxS synthase suggesting that this genus plays an important role in QS within the rumen.

Conclusion

This is the most comprehensive study of QS in the rumen microbiome to date. This study shows that AI-2-based QS is rife in the rumen. These results allow a greater understanding on plant-microbe interactions in the rumen.
Effects of microplastics and salinity on food waste processing by black soldier fly (Hermetia illucens) larvae
Authors: Cho Sam , Kim Chul-Hwan , Kim Min-Ji , Chung Haegeun
Published: February 2020

Background

The black soldier fly (Hermetia illucens) is gaining attention as an efficient decomposer of food waste. However, recalcitrant compounds such as plastics mixed into food waste may have negative effects on its growth and survival. Moreover, its efficiency of food waste degradation may also be affected by plastics. In addition, salt (NaCl) can also be present in high concentrations, which also reduces the efficiency of H. illucens-mediated food waste treatment. In this study, we assessed the growth of black soldier fly larvae (BSFL) reared on food waste containing polyethylene (PE) and polystyrene (PS) and NaCl. The weight of BSFL was measured every 2–4 days. Survival and substrate reduction rates and pupation ratio were determined at the end of the experiment.

Results

The total larval weight of Hermetia illucens reared on food waste containing PS was greater than that of the control on days 20 and 24. However, the survival rate was lower in the group treated with 5% PS, as was substrate reduction in all PS-treated groups. The weight of BSFL reared on food waste containing PE was lower than that of the control on day 6. PE in food waste did not affect the survival rate, but the pupation ratio increased and substrate consumption decreased with increasing PE concentrations. Regardless of the plastic type, the addition of NaCl resulted in decreased larval weight and pupation ratio.

Conclusions

Larval growth of black soldier fly was inhibited not by plastics but by substrate salinity. Additional safety assessments of larvae reared on food waste containing impurities are needed to enable wider application of BSFL in vermicomposting.
Clinical and Genetic Risk Prediction of Cognitive Impairment After Blood or Marrow Transplantation for Hematologic Malignancy
Authors: Sharafeldin Noha , Richman Joshua , Bosworth Alysia , Chen Yanjun , Singh Purnima , Patel Sunita K. , Wang Xuexia , Francisco Liton , Forman Stephen J. , Wong F. Lennie , Bhatia Smita
Published: February 2020

PURPOSE

Using a candidate gene approach, we tested the hypothesis that individual single nucleotide polymorphisms (SNPs) and gene-level variants are associated with cognitive impairment in patients with hematologic malignancies treated with blood or marrow transplantation (BMT) and that inclusion of these SNPs improves risk prediction beyond that offered by clinical and demographic characteristics.

PATIENTS AND METHODS

In the discovery cohort, BMT recipients underwent a standardized battery of neuropsychological tests pre-BMT and at 6 months, 1 year, 2 years, and 3 years post-BMT. Associations between 68 candidate genes and cognitive impairment were assessed using generalized estimating equation models. Elastic-Net regression was used to build Base (sociodemographic), Clinical, and Combined (Base plus Clinical plus genetic) risk prediction models of post-BMT impairment. An independent nonoverlapping cohort from the BMT Survivor Study with self-report of learning/memory problems (as identified by their health care provider) was used for model replication.

RESULTS

The discovery cohort included 277 participants (58.5% males; 68.6% non-Hispanic whites; and 46.6% allogeneic BMT recipients). Adjusting for BMT type, age at BMT, sex, race/ethnicity, and cognitive reserve, SNPs in the blood-brain barrier, telomere homeostasis, and DNA repair genes were significantly associated with cognitive impairment. Compared with the Clinical Model, the Combined Model had higher predictive power in both the discovery cohort (mean area under the receiver operating characteristic curve [AUC], 0.89; 95% CI, 0.85 to 0.93 v 0.77; 95% CI, 0.71 to 0.83; P = 1.24 × 10−9) and the replication cohort (AUC, 0.71; 95% CI, 0.66 to 0.76 v 0.63; 95% CI, 0.57 to 0.68; P = .004).

CONCLUSION

Inclusion of candidate genetic variants enhanced the prediction of risk of post-BMT cognitive impairment beyond that offered by demographic/clinical characteristics and represents a step toward a personalized approach to managing patients at high risk for cognitive impairment after BMT.
State-of-the-Art Strategies for Targeting RET-Dependent Cancers
Authors: Subbiah Vivek , Yang Dong , Velcheti Vamsidhar , Drilon Alexander , Meric-Bernstam Funda
Published: February 2020

Activating receptor tyrosine kinase RET (rarranged during transfection) gene alterations have been identified as oncogenic in multiple malignancies. RET gene rearrangements retaining the kinase domain are oncogenic drivers in papillary thyroid cancer, non–small-cell lung cancer, and multiple other cancers. Activating RET mutations are associated with different phenotypes of multiple endocrine neoplasia type 2 as well as sporadic medullary thyroid cancer. RET is thus an attractive therapeutic target in patients with oncogenic RET alterations. Multikinase inhibitors with RET inhibitor activity, such as cabozantinib and vandetanib, have been explored in the clinic for tumors with activating RET gene alterations with modest clinical efficacy. As a result of the nonselective nature of these multikinase inhibitors, patients had off-target adverse effects, such as hypertension, rash, and diarrhea. This resulted in a narrow therapeutic index of these drugs, limiting ability to dose for clinically effective RET inhibition. In contrast, the recent discovery and clinical validation of highly potent selective RET inhibitors (pralsetinib, selpercatinib) demonstrating improved efficacy and a more favorable toxicity profile are poised to alter the landscape of RET-dependent cancers. These drugs appear to have broad activity across tumors with activating RET alterations. The mechanisms of resistance to these next-generation highly selective RET inhibitors is an area of active research. This review summarizes the current understanding of RET alterations and the state-of-the-art treatment strategies in RET-dependent cancers.
Putting The Pieces Together Again: American States and the End of the ACA's Shared Responsibility Payment
Authors: Gais Thomas L. , Gusmano Michael K.
Published: February 2020

The Tax Cuts and Jobs Act (TCJA) eliminated the ACA's “shared responsibility payment,” which penalized those who failed to comply with the requirement to purchase health insurance. In this article the authors explain efforts in several states to respond to this change by adopting individual health insurance mandates at the state level. Although there are good reasons to think that states may be reluctant to consider establishing their own mandates, New Jersey, the District of Columbia, and Vermont quickly joined Massachusetts in establishing such measures in 2018. In 2019 California and Rhode Island enacted state-level mandates. Four other states—Maryland, Connecticut, Hawaii, and Washington—formally considered mandates but have not enacted them. The authors compare the policy debates among these states and one other state, New York, which has not seen a legislative proposal for a mandate despite its strong support for the ACA. Their analysis explores the dynamics within the US federal system when a key component of a complex and politically salient national initiative is eliminated and states are left with many policy, political, and administrative questions of what to do next.
Molecular regulation of the plasma membrane-proximal cellular steps involved in NK cell cytolytic function
Authors: Phatarpekar Prasad V. , Billadeau Daniel D.
Published: February 2020

Natural killer (NK) cells, cytolytic lymphocytes of the innate immune system, play a crucial role in the immune response against infection and cancer. NK cells kill target cells through exocytosis of lytic granules that contain cytotoxic proteins, such as perforin and granzymes. Formation of a functional immune synapse, i.e. the interface between the NK cell and its target cell enhances lysis through accumulation of polymerized F-actin at the NK cell synapse, leading to convergence of lytic granules to the microtubule organizing center (MTOC) and its subsequent polarization along microtubules to deliver the lytic granules to the synapse. In this review, we focus on the molecular mechanisms regulating the cellular processes that occur after the lytic granules are delivered to the cytotoxic synapse. We outline how – once near the synapse – the granules traverse the clearings created by F-actin remodeling to dock, tether and fuse with the plasma membrane in order to secrete their lytic content into the synaptic cleft through exocytosis. Further emphasis is given to the role of Ca2+ mobilization during degranulation and, whenever applicable, we compare these mechanisms in NK cells and cytotoxic T lymphocytes (CTLs) as adaptive immune system effectors.
Lower-Limb Biomechanics in Football Players with and without Hip-related Pain
Authors: KING MATTHEW G. , SEMCIW ADAM I. , SCHACHE ANTHONY G. , MIDDLETON KANE J. , HEEREY JOSHUA J. , SRITHARAN PRASANNA , SCHOLES MARK J. , MENTIPLAY BENJAMIN F. , CROSSLEY KAY M.
Published: February 2020

Purpose

This study aimed to evaluate the differences in lower-limb biomechanics between adult subelite competitive football players with and without hip-related pain during two contrasting tasks—walking and single-leg drop jump (SLDJ)—and to determine whether potential differences, if present, are sex dependent.

Methods

Eighty-eight football players with hip-related pain (23 women, 65 men) and 30 asymptomatic control football players (13 women, 17 men) who were currently participating in competitive sport were recruited. Biomechanical data were collected for the stance phase of walking and SLDJ. Pelvis, hip, knee, and ankle angles, as well as the impulse of the external joint moments, were calculated. Differences between groups and sex-specific effects were calculated using linear regression models.

Results

Compared with their asymptomatic counterparts, football players with hip-related pain displayed a lower average pelvic drop angle during walking (P = 0.03) and a greater average pelvic hike angle during SLDJ (P < 0.05). Men with hip-related pain displayed a smaller total range of motion (excursion) for the transverse plane pelvis angle (P = 0.03) and a smaller impulse of the hip external rotation moment (P < 0.01) during walking compared with asymptomatic men. Women with hip-related pain displayed a greater total range of motion (excursion) for the sagittal plane knee angle (P = 0.01) during walking compared with asymptomatic women.

Conclusion

Overall, few differences were observed in lower-limb biomechanics between football players with and without hip-related pain, irrespective of the task. This outcome suggests that, despite the presence of symptoms, impairments in lower-limb biomechanics during function do not appear to be a prominent feature of people with hip-related pain who are still participating in sport.
Profiles of Heart Rate Variability and Bar Velocity after Resistance Exercise
Authors: DOBBS WARD C. , FEDEWA MICHAEL V. , MACDONALD HAYLEY V. , TOLUSSO DANILO V. , ESCO MICHAEL R.
Published: February 2020

Introduction

The aim of this investigation was to observe the association in the time course in recovery between multiple heart rate variability (HRV) metrics and neuromuscular performance, as assessed by mean bar velocity (BVM) in the back squat, over a 72-h period after an exhaustive back squat protocol.

Methods

Eight resistance-trained males completed five laboratory visits within a 7-d period. The first visit involved short-term HRV recordings followed by a familiarization of BVM procedures and a one-repetition maximum test of the back squat. Forty-eight hours later, participants returned to the laboratory for prestimulus measurements, immediately followed by a back squat protocol (8 sets of 10 repetitions at 70% of one-repetition maximum with a 2-min rest). The HRV and the BVM measurements were replicated at 0.5, 24, 48, and 72 h after squat protocol. A multivariate profile analysis and repeated-measures correlation between recovery scores [(new/prestimulus) × 100] for each HRV metric and BVM was computed.

Results

All log-transformed (ln) HRV metrics, except low frequency (lnLF) (P = 0.051), had a significant interaction with BVM over time (P < 0.05), indicating that recovery scores in BVM and HRV were not parallel. In addition, recovery scores in all HRV metrics significantly differed from BVM (P < 0.05) in at least one time point across the 72-h period. Furthermore, repeated-measures correlation analysis indicated a lack of intraindividual association (P > 0.05) between the change in BVM and all HRV measurements over time.

Conclusion

The time course in recovery in HRV measurements after an exhaustive bout of lower-body resistance exercise was not associated with neuromuscular performance recovery.
Leucine Supplementation Has No Further Effect on Training-induced Muscle Adaptations
Authors: DE ANDRADE ISABEL THOMAZI , GUALANO BRUNO , HEVIA-LARRAÍN VICTORIA , NEVES-JUNIOR JUAREZ , CAJUEIRO MONIQUE , JARDIM FELIPE , GOMES RODRIGO LEITE , ARTIOLI GUILHERME GIANNINI , PHILLIPS STUART M. , CAMPOS-FERRAZ PATRÍCIA , ROSCHEL HAMILTON
Published: February 2020

Introduction

Several acute studies have suggested that leucine is a key amino acid to drive muscle protein synthesis. However, there are very few studies on the long-term effects of leucine supplementation on resistance training (RT)–induced gains in muscle mass and strength. We sought to determine the impact of 10 g of leucine on muscle mass and strength in response to RT in healthy young men.

Methods

Twenty-five, resistance-trained men (27 ± 5 yr; 78.4 ± 11.6 kg; 24.8 ± 3.0 kg·m−2) consuming 1.8 ± 0.4 g protein·kg−1·d−1, were randomly assigned to receive 2 × 5 g·d−1 supplementation of either free leucine (LEU n = 12) or alanine (PLA n = 13) while undergoing a supervised 12-wk, twice-weekly lower-limb RT program. One-repetition maximum (leg-press 1RM) and muscle cross-sectional area (mCSA) of the vastus lateralis were determined before (PRE) and after (POST) the intervention. Additionally, three 24-h dietary recalls were also performed at PRE and POST.

Results

Protein intake was roughly double that of the RDA in both groups and remained unchanged across time with no differences detected between groups. Similar increases were observed between groups in leg-press 1RM (LEU, 19.0% ± 9.4% and PLA, 21.0% ± 10.4%, P = 0.31) and mCSA (LEU, 8.0% ± 5.6% and PLA, 8.4% ± 5.1%, P = 0.77).

Conclusions

High-dose leucine supplementation did not enhance gains in muscle strength and mass after a 12-wk RT program in young resistance-trained males consuming adequate amounts of dietary protein.
Physical Activity and Mortality among Male Survivors of Myocardial Infarction
Authors: AL-SHAAR LAILA , LI YANPING , RIMM ERIC B. , MANSON JOANN E. , ROSNER BERNARD , HU FRANK B. , STAMPFER MEIR J. , WILLETT WALTER C.
Published: February 2020

Purpose

An inverse association between physical activity (PA) and risk of CHD has been seen in many studies, but evidence for benefits of PA after myocardial infarction (MI) in reducing mortality is limited.

Methods

Using data from the Health Professionals Follow-up Study cohort, we followed male survivors of MI. Short- and long-term changes in PA from before to after MI were calculated, and participants without ambulation impairment were classified into maintained low, decreased, increased, or maintained high PA categories. Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality across PA and PA change categories.

Results

During a mean of 14 yr of follow-up of 1651 incident nonfatal MI cases, we documented 678 deaths, 307 were due to cardiovascular disease. The adjusted HR for all-cause mortality comparing ≥21 with ≤1.5 MET·wk−1 of PA before MI was 0.73 (95% CI = 0.59–0.89, P
trend = 0.03). Compared with men who maintained low PA before and after MI, men who maintained high PA had a 39% (95% CI = 25–50) lower risk of all-cause mortality, and those who had a long-term increase in PA from before to after MI had a 27% (95% CI = 6–43) lower risk. Walking for ≥30 min·d−1 after MI was associated with a 29% lower mortality (HR = 0.71, 95% CI = 0.58–0.84), independent of walking pace, and walking pace after MI was inversely associated with mortality (HR = 0.67, 95% CI = 0.49–0.92).

Conclusions

Maintaining a high PA or having a long-term increase in PA from before to after MI was associated with lower mortality among male MI survivors. Walking time and walking pace after MI were each inversely associated with mortality.
Exercise Induces Different Molecular Responses in Trained and Untrained Human Muscle
Authors: MOBERG MARCUS , LINDHOLM MALENE E. , REITZNER STEFAN M. , EKBLOM BJÖRN , SUNDBERG CARL-JOHAN , PSILANDER NIKLAS
Published: February 2020

Introduction

Human skeletal muscle is thought to have heightened sensitivity to exercise stimulus when it has been previously trained (i.e., it possesses “muscle memory”). We investigated whether basal and acute resistance exercise-induced gene expression and cell signaling events are influenced by previous strength training history.

Methods

Accordingly, 19 training naïve women and men completed 10 wk of unilateral leg strength training, followed by 20 wk of detraining. Subsequently, an acute resistance exercise session was performed for both legs, with vastus lateralis biopsies taken at rest and 1 h after exercise in both legs (memory and control).

Results

The phosphorylation of AMPKThr172 and eEF2Thr56 was higher in the memory leg than that in the control leg at both time points. The postexercise phosphorylation of 4E-BP1Thr46 and Ser65 was higher in the memory leg than that in the control leg. The memory leg had lower basal mRNA levels of total PGC1α and, unlike the control leg, exhibited increases in PGC1α-ex1a transcripts after exercise. In the genes related to myogenesis (SETD3, MYOD1, and MYOG), mRNA levels differed between the memory and the untrained leg; these effects were evident primarily in the male subjects. Expression of the novel gene SPRYD7 was lower in the memory leg at rest and decreased after exercise only in the control leg, but SPRYD7 protein levels were higher in the memory leg.

Conclusion

In conclusion, several key regulatory genes and proteins involved in muscular adaptations to resistance exercise are influenced by previous training history. Although the relevance and mechanistic explanation for these findings need further investigation, they support the view of a molecular muscle memory in response to training.
Nrf2 Activation Enhances Muscular MCT1 Expression and Hypoxic Exercise Capacity
Authors: WANG LINJIA , ZHU RONGXIN , WANG JIAHUI , YU SIWANG , WANG JIANXIONG , ZHANG YING
Published: February 2020

Introduction

Skeletal muscle is the major producing and metabolizing site of lactic acid. A family of monocarboxylate transporter (MCT) proteins, especially MCT1 and MCT4, are involved in the lactate–pyruvate exchange and metabolism. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal coordinator of antioxidant response and energy metabolism, and has been reported to associate with the physiological functions of the skeletal muscle.

Methods

In this study, C57BL/6 J mice were administrated with an Nrf2 activator, sulforaphane (SFN) before taking incremental treadmill exercise to exhaustion under hypoxia; then the effects of SFN on exercise endurance and molecular/biochemical makers of the skeletal muscle were evaluated.

Results

The results indicated that SFN pretreatment enhanced the exercise endurance under hypoxia. SFN not only increased the expressions of antioxidant genes and activity of antioxidant enzymes, but also significantly increased the mRNA and protein levels of MCT1 and CD147, but not MCT4. Moreover, the expressions of LDH-B and LDH activity of converting lactate into pyruvate, as well as citrate synthase activity were significantly higher, whereas the LDH activity of converting pyruvate into lactate and blood lactate level were remarkably lower in the SFN-exercise mice than those of the phosphate-buffered saline–exercise group. Furthermore, Atf3Δzip2 (the alternatively spliced isoform of activating transcription factor-3) mRNA was increased by the exercise and further potentiated by SFN.

Conclusion

These results show, for the first time, that SFN increases MCT1 expression in the skeletal muscle under acute hypoxic exercise and suggest that Nrf2 activation is a promising strategy to enhance exercise performance under hypoxia.
Διαδίκτυο και Ενημέρωση: προβλήματα και εκπαίδευση
Authors: Θεοφανέλλης Τιμολέων Νικόλαος , Αντίκα Μαρία
Published: February 2020

Ο ερχομός του διαδικτύου στην ενημέρωση αναμενόταν να φέρει πολυφωνία και αντικειμενικότητα. Ωστόσο, φαινόμενα όπως οι ψευδής ειδήσεις (fake news), ο αντίλαλος (echo chamber) και η φιλτραρισμένη φούσκα (filter bubble) αξιοποιώντας ανθρώπινες αδυναμίες απλά ενίσχυσαν τα δεδομένα που υπήρχαν πριν την έλευση του διαδικτύου. Τα φαινόμενα αυτά ενισχύονται μέσα από αλγορίθμους που χρησιμοποιούν ιστότοποι για να παρέχουν δωρεάν υπηρεσίες στους χρήστες, ενώ παράλληλα έχουν κέρδος από την προσέλκυση και την παραμονή των χρηστών σε αυτές. Παρόλα αυτά στο διαδίκτυο υπάρχει πολυφωνία, αλλά για να φτάσουμε σε αυτή χρειάζεται να αναγνωρίσουμε αυτά τα φαινόμενα, να ευαισθητοποιηθούμε απέναντι τους και να εκπαιδευτούμε ώστε να καταφέρουμε να φτάσουμε στην αντικειμενική και πολυφωνική ενημέρωση. Είναι απαραίτητα να είμαστε κριτικοί σε αυτά που ακούμε και διαβάζουμε προκειμένου να είμαστε σε θέση να ασκήσουμε μεγαλύτερο έλεγχο στο μέλλον μας σε σχέση με τους ανθρώπους που δεν διαθέτουν αυτή τη γνώση.
Σχολική εξ αποστάσεως εκπαίδευση: μελέτη περίπτωσης με το σχεδιασμό, την ανάπτυξη και αρχική αποτίμηση του εκπαιδευτικού υλικού για τη διδασκαλία της ενότητας της κινηματικής στη Φυσική της Α’ Λυκείου
Authors: Σταυγιαννουδάκης Στυλιανός , Καλογιαννάκης Μιχάλης
Published: February 2020

Στο πλαίσιο της παρούσας έρευνας δημιουργήθηκε μαθησιακό υλικό με τη μεθοδολογία της εξ αποστάσεως εκπαίδευσης για το μάθημα της φυσικής της Α’ Λυκείου. Το υλικό χρησιμοποιήθηκε για την επαναληπτική διδασκαλία της ενότητας των κινήσεων βάσει του επίσημου αναλυτικού προγράμματος σπουδών και απευθυνόταν σε μαθητές Γενικού Λυκείου. Η ερευνητική διαδικασία είχε βασικό σκοπό την ανίχνευση του βαθμού ικανοποίησης των μαθητών ενός απομακρυσμένου Γενικού Λυκείου του Νομού Χανίων από την παρακολούθηση του εξ αποστάσεως υλικού στο σύστημα διαχείρισης μάθησης Chamillo. Η εξ αποστάσεως συμπληρωματική σχολική εκπαίδευση μελετήθηκε βάσει εννέα θεματικών αξόνων σύμφωνα με τα κριτήρια ποιότητας που επιλέχθηκαν έπειτα από τη σχετική βιβλιογραφική επισκόπηση. Τα αποτελέσματα της έρευνας ανέδειξαν τη θετική στάση των μαθητών απέναντι στην εξ αποστάσεως σχολική εκπαίδευση και το συγκεκριμένο υλικό για το μάθημα της φυσικής. Το στοιχείο αυτό ενισχύει την περαιτέρω διαμορφωτική αξιολόγηση ολόκληρης της εκπαιδευτικής διαδικασίας, ώστε να εμπλουτιστεί, προκειμένου να καλύψει τις πραγματικές ανάγκες των μαθητών, όπως προκύπτουν από τη φυσική απόστασή τους από το σχολικό περιβάλλον.