bluuebunny/crossref_metadata_2025 huggingface dataset:
FastMM: an efficient toolbox for personalized constraint-based metabolic modeling
Authors: Li Gong-Hua , Dai Shaoxing , Han Feifei , Li Wenxing , Huang Jingfei , Xiao Wenzhong
Published: February 2020

Background

Constraint-based metabolic modeling has been applied to understand metabolism related disease mechanisms, to predict potential new drug targets and anti-metabolites, and to identify biomarkers of complex diseases. Although the state-of-art modeling toolbox, COBRA 3.0, is powerful, it requires substantial computing time conducting flux balance analysis, knockout analysis, and Markov Chain Monte Carlo (MCMC) sampling, which may limit its application in large scale genome-wide analysis.

Results

Here, we rewrote the underlying code of COBRA 3.0 using C/C++, and developed a toolbox, termed FastMM, to effectively conduct constraint-based metabolic modeling. The results showed that FastMM is 2~400 times faster than COBRA 3.0 in performing flux balance analysis and knockout analysis and returns consistent outputs. When applied to MCMC sampling, FastMM is 8 times faster than COBRA 3.0. FastMM is also faster than some efficient metabolic modeling applications, such as Cobrapy and Fast-SL. In addition, we developed a Matlab/Octave interface for fast metabolic modeling. This interface was fully compatible with COBRA 3.0, enabling users to easily perform complex applications for metabolic modeling. For example, users who do not have deep constraint-based metabolic model knowledge can just type one command in Matlab/Octave to perform personalized metabolic modeling. Users can also use the advance and multiple threading parameters for complex metabolic modeling. Thus, we provided an efficient and user-friendly solution to perform large scale genome-wide metabolic modeling. For example, FastMM can be applied to the modeling of individual cancer metabolic profiles of hundreds to thousands of samples in the Cancer Genome Atlas (TCGA).

Conclusion

FastMM is an efficient and user-friendly toolbox for large-scale personalized constraint-based metabolic modeling. It can serve as a complementary and invaluable improvement to the existing functionalities in COBRA 3.0. FastMM is under GPL license and can be freely available at GitHub site: https://github.com/GonghuaLi/FastMM.
Heterosis analysis and underlying molecular regulatory mechanism in a wide-compatible neo-tetraploid rice line with long panicles
Authors: Ghaleb Mohammed Abdullah Abdulraheem , Li Cong , Shahid Muhammad Qasim , Yu Hang , Liang Junhong , Chen Ruoxin , Wu Jinwen , Liu Xiangdong
Published: February 2020

Background

Neo-tetraploid rice, which is a new germplasm developed from autotetraploid rice, has a powerful biological and yield potential and could be used for commercial utilization. The length of panicle, as a part of rice panicle architecture, contributes greatly to high yield. However, little information about long panicle associated with heterosis or hybrid vigor is available in neo-tetraploid rice.

Results

In the present study, we developed a neo-tetraploid rice line, Huaduo 8 (H8), with long panicles and harboring wide-compatibility genes for pollen and embryo sac fertility. All the hybrids generated by H8 produced significant high-parent yield heterosis and displayed long panicles similar to H8. RNA-seq analysis detected a total of 4013, 7050, 6787 and 6195 differentially expressed genes uniquely belonging to F1 and specifically (DEGFu-sp) associated with leaf, sheath, main panicle axis and spikelet in the two hybrids, respectively. Of these DEGFu-sp, 279 and 89 genes were involved in kinase and synthase, and 714 cloned genes, such as GW8, OsGA20ox1, Ghd8, GW6a, and LP1, were identified and validated by qRT-PCR. A total of 2925 known QTLs intervals, with an average of 1~100 genes per interval, were detected in both hybrids. Of these, 109 yield-related QTLs were associated with seven important traits in rice. Moreover, 1393 non-additive DEGs, including 766 up-regulated and 627 down-regulated, were detected in both hybrids. Importantly, eight up-regulated genes associated with panicle were detected in young panicles of the two hybrids compared to their parents by qRT-PCR. Re-sequencing analysis depicted that LP (a gene controlling long panicle) sequence of H8 was different from many other neo-tetraploid rice and most of the diploid and autotetraploid lines. The qRT-PCR results showed that LP was up-regulated in the hybrid compared to its parents at very young stage of panicle development.

Conclusions

These results suggested that H8 could overcome the intersubspecific autotetraploid hybrid rice sterility caused by embryo sac and pollen sterility loci. Notably, long panicles of H8 showed dominance phenomenon and played an important role in yield heterosis, which is a complex molecular mechanism. The neo-tetraploid rice is a useful germplasm to attain high yield of polyploid rice.
Cytotoxicity of amide-linked local anesthetics on melanoma cells via inhibition of Ras and RhoA signaling independent of sodium channel blockade
Authors: Zheng Qinghong , Peng Xiaohong , Zhang Yaqin
Published: February 2020

Background

Substantial clinical and preclinical evidence have indicated the association between amide-linked local anesthesia and the long-term outcomes of cancer patients. However, the potential effects of local anesthesia on cancer recurrence are inconclusive and the underlying mechanisms remain poorly understood.

Methods

We systematically examined the effects of three commonly used local anesthetics in melanoma cells and analyzed the underlying mechanisms focusing on small GTPases.

Results

Ropivacaine and lidocaine but not bupivacaine inhibited migration and proliferation, and induced apoptosis in melanoma cells. In addition, ropivacaine and lidocaine but not bupivacaine significantly augmented the in vitro efficacy of vemurafenib (a B-Raf inhibitor for melanoma with BRAF V600E mutation) and dacarbazine (a chemotherapeutic drug). Mechanistically, ropivacaine but not bupivacaine decreased the activities of Ras superfamily members with the dominant inhibitory effects on RhoA and Ras, independent of sodium channel blockade. Rescue studies using constitutively active Ras and Rho activator calpeptin demonstrated that ropivacaine inhibited migration mainly through RhoA whereas growth and survival were mainly inhibited through Ras in melanoma cells. We further detected a global reduction of downstream signaling of Ras and RhoA in ropivacaine-treated melanoma cells.

Conclusion

Our study is the first to demonstrate the anti-melanoma activity of ropivacaine and lidocaine but not bupivacaine, via targeting small GTPases. Our findings provide preclinical evidence on how amide-linked local anesthetics could affect melanoma patients.
Sepsis in cancer patients residing in Zimbabwe: spectrum of bacterial and fungal aetiologies and their antimicrobial susceptibility patterns
Authors: Chinowaita Frank , Chaka Wendy , Nyazika Tinashe K. , Maboreke Tendai C. , Tizauone Emmanuel , Mapondera Prichard , Chitsike Inam , Cakana Andrew Z. , Mavenyengwa Rooyen T.
Published: February 2020

Background

Cancer and sepsis comorbidity is a major public health problem in most parts of the world including Zimbabwe. The microbial aetiologies of sepsis and their antibiograms vary with time and locations. Knowledge on local microbial aetiologies of sepsis and their susceptibility patterns is critical in guiding empirical antimicrobial treatment choices.

Methods

This was a descriptive cross-sectional study which determined the microbial aetiologies of sepsis from blood cultures of paediatric and adult cancer patients obtained between July 2016 and June 2017. The TDR-X120 blood culture system and TDR 300B auto identification machine were used for incubation of blood culture bottles and identification plus antimicrobial susceptibility testing, respectively.

Results

A total of 142 participants were enrolled; 50 (35.2%) had positive blood cultures, with 56.0% Gram positive, 42.0% Gram-negative bacteria and 2.0% yeast isolated. Common species isolated included coagulase negative Staphylococcus spp. (CoNS) (22.0%), E. coli (16.0%), K. pneumoniae (14.0%), E. faecalis (14.0%) and S. aureus (8.0%). Gram-negative isolates exhibited high resistance to gentamicin (61.9%) and ceftriaxone (71.4%) which are the empiric antimicrobial agents used in our setting. Amikacin and meropenem showed 85.7 and 95.2% activity respectively against all Gram-negative isolates, whilst vancomycin and linezolid were effective against 96.2 and 100.0% of all Gram-positive isolates respectively. We isolated 10 (66.7%) extended spectrum β-lactamase (ESBL) amongst the E. coli and K. pneumoniae isolates. Ten (66.7%) of the Staphylococcus spp. were methicillin resistant.

Conclusions

CoNS, E. coli, K. pneumoniae, E. faecalis and S. aureus were the major microbial drivers of sepsis amongst cancer patients in Zimbabwe. Most isolates were found to be resistant to commonly used empirical antibiotics, with isolates exhibiting high levels of ESBL and methicillin resistance carriage. A nationwide survey on microbial aetiologies of sepsis and their susceptibility patterns would assist in the guidance of effective sepsis empiric antimicrobial treatment among patients with cancer.
Prune belly syndrome in surviving males can be caused by Hemizygous missense mutations in the X-linked Filamin A gene
Authors: Iqbal Nida S. , Jascur Thomas A. , Harrison Steven M. , Edwards Angelena B. , Smith Luke T. , Choi Erin S. , Arevalo Michelle K. , Chen Catherine , Zhang Shaohua , Kern Adam J. , Scheuerle Angela E. , Sanchez Emma J. , Xing Chao , Baker Linda A.
Published: February 2020

Background

Prune belly syndrome (PBS) is a rare, multi-system congenital myopathy primarily affecting males that is poorly described genetically. Phenotypically, its morbidity spans from mild to lethal, however, all isolated PBS cases manifest three cardinal pathological features: 1) wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, 2) urinary tract dilation with poorly contractile smooth muscle, and 3) intra-abdominal undescended testes. Despite evidence for a genetic basis, previously reported PBS autosomal candidate genes only account for one consanguineous family and single cases.

Methods

We performed whole exome sequencing (WES) of two maternal adult half-brothers with syndromic PBS (PBS + Otopalatodigital spectrum disorder [OPDSD]) and two unrelated sporadic individuals with isolated PBS and further functionally validated the identified mutations.

Results

We identified three unreported hemizygous missense point mutations in the X-chromosome gene Filamin A (FLNA) (c.4952 C > T (p.A1448V), c.6727C > T (p.C2160R), c.5966 G > A (p.G2236E)) in two related cases and two unrelated sporadic individuals. Two of the three PBS mutations map to the highly regulatory, stretch-sensing Ig19–21 region of FLNA and enhance binding to intracellular tails of the transmembrane receptor β-integrin 1 (ITGβ1).

Conclusions

FLNA is a regulatory actin-crosslinking protein that functions in smooth muscle cells as a mechanosensing molecular scaffold, transmitting force signals from the actin-myosin motor units and cytoskeleton via binding partners to the extracellular matrix. This is the first evidence for an X-linked cause of PBS in multiple unrelated individuals and expands the phenotypic spectrum associated with FLNA in males surviving even into adulthood.
Maternal and child-health outcomes in pregnancies following Assisted Reproductive Technology (ART): a prospective cohort study
Authors: da Silva Shana Ginar , da Silveira Mariângela Freitas , Bertoldi Andréa Dâmaso , Domingues Marlos Rodrigues , dos Santos Iná da Silva
Published: February 2020

Background

Studies comparing the outcome of spontaneous versus assisted reproductive technologies (ART) pregnancies report heterogeneous results. Despite the success of ART to overcome infertility, concern is growing regarding both its safety and its effect on maternal and child health. The objective of this study was to compare maternal and child-health outcomes after ART relative to natural conception.

Methods

A population-based birth cohort study was carried out among pregnant women expected to deliver in 2015 in Pelotas, southern Brazil. Maternal outcomes included pregnancy complications and gestational weight gain. Gestational age, weight, intrauterine growth restriction, length and head circumference, and 1-min and 5-min Apgar, as well as health problems at birth and breastfeeding were defined as offspring outcomes. Statistical analyses were performed using linear and logistic regression. G-formula was used to perform mediation analysis.

Results

The study included 4252 babies born by spontaneously pregnancies and 23 babies born after ART. Adjusted analyses showed that children conceived from ART presented lower means of gestational age (p = 0.001), birth weight (p = 0.002), length (p < 0.001), and head circumference at birth (p = 0.02). However, more than 90% of the effect of ART over these outcomes was mediated by multiple pregnancy.

Conclusion

Our findings suggest that the possible negative effect on the child-health outcomes is due mainly to the higher incidence of multiple pregnancies and not because of ART. The reasons for the increase in adverse pregnancy outcomes associated with ART singleton pregnancies are still uncertain and warrants further research. Further large-population studies are needed to confirm these results.
Maternal coffee intake and the risk of bleeding in early pregnancy: a cross-sectional analysis
Authors: Choi Hansol , Koo Seul , Park Hyun-Young
Published: February 2020

Background

Caffeine can easily cross the placenta, and maternal caffeine intake, thus, has an effect on fetal growth. However, it is still unclear whether coffee consumption is an independent risk factor for bleeding in early pregnancy. The objective of this study was to examine the association between pre-pregnancy coffee consumption patterns and the risk of bleeding in early pregnancy.

Methods

A cross-sectional analysis was conducted among 3510 pregnant women from the Korean Pregnancy Outcome Study who underwent baseline examination and for whom the results of the pregnancy were available. Coffee consumption patterns before pregnancy were examined using a questionnaire. The participants were classified according to the frequency of coffee consumption into seldom (< 1 cup/week), light (< 1 cup/day), moderate (1 cup/day), and heavy coffee drinker (≥2 cups/day) groups. Bleeding in early pregnancy was defined as the occurrence of vaginal bleeding in the first 20 weeks of pregnancy. Multiple logistic regression models were applied to examine the association between pre-pregnancy coffee consumption and the risk of bleeding in early pregnancy, after adjusting for age, body mass index (BMI), systolic blood pressure, cigarette smoking and alcohol consumption behavior, previous and current physical activity levels, stress levels, history of depression, antenatal depressive symptoms during the first trimester, type of emesis, parity, and the number of livebirths, stillbirths, miscarriages, and abortions.

Results

Women who were light, moderate, and heavy coffee drinkers before pregnancy had adjusted ORs of 1.086, 1.225, and 1.358, respectively, for bleeding in early pregnancy. In a fully adjusted model, heavy coffee drinkers showed a significantly higher risk of bleeding in early pregnancy, even in women aged 35 years and younger (OR 1.680) and in those with a normal body mass index (OR 1.389), who were at relatively low risk for pregnancy-related complications.

Conclusions

Our results showed that heavy coffee drinking was independently associated with a higher risk of bleeding in early pregnancy among pregnant Korean women, suggesting that caffeine intake before conception and during pregnancy should be reduced. Our study highlights the need for nutritional interventions for healthy coffee drinking among pregnant women in Korea.
Blood test shows high accuracy in detecting stage I non-small cell lung cancer
Authors: Goebel Cherylle , Louden Christopher L. , Mckenna Robert , Onugha Osita , Wachtel Andrew , Long Thomas
Published: February 2020

Background

In a previous study (Goebel et. al, Cancer Genomics Proteomics 16:229-244, 2019), we identified 33 biomarkers for an early stage (I-II) Non-Small Cell Lung Cancer (NSCLC) test with 90% accuracy, 80.3% sensitivity, and 95.4% specificity. For the current study, we used a narrowed ensemble of 21 biomarkers while retaining similar accuracy in detecting early stage lung cancer.

Methods

A multiplex platform, 486 human plasma samples, and 21 biomarkers were used to develop and validate our algorithm which detects early stage NSCLC. The training set consisted of 258 human plasma with 79 Stage I-II NSCLC samples. The 21 biomarkers with the statistical model (Lung Cancer Detector Test 1, LCDT1) was then validated using 228 novel samples which included 55 Stage I NSCLC.

Results

The LCDT1 exhibited 95.6% accuracy, 89.1% sensitivity, and 97.7% specificity in detecting Stage I NSCLC on the blind set. When only NSCLC cancers were analyzed, the specificity increased to 99.1%.

Conclusions

Compared to current approved clinical methods for diagnosing NSCLC, the LCDT1 greatly improves accuracy while being non-invasive; a simple, cost-effective, early diagnostic blood test should result in expanding access and increase survival rate.
Perceived occurrence of an adverse event affects patient-reported outcomes after total hip replacement
Authors: Carpenter Charlotte V. E. , Wylde Vikki , Moore Andrew J. , Sayers Adrian , Blom Ashley W. , Whitehouse Michael R.
Published: February 2020

Background

Dislocation, periprosthetic fracture and infection are serious complications of total hip replacement (THR) and which negatively impact on patients’ outcomes including satisfaction, quality of life, mental health and function. The accuracy with which patients report adverse events (AEs) after surgery varies. The impact of patient self-reporting of AEs on patient-reported outcome measures (PROMs) after THR is yet to be investigated. Our aim was to determine the effect of confirmed and perceived AEs on PROMs after primary THR.

Methods

A prospective single-centre cohort study of patients undergoing primary THR, with one-year follow-up, was performed. Participants completed forms pre-operatively and 3, 6, 9 and 12 months post-operatively, including Work Productivity and Activity Impairment (WPAI), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol-5D-3 L (EQ5D), Self-Administered Patient Satisfaction (SAPS) and AE reporting questionnaires. Results were reported in three groups: No AE, reported but not confirmed AE and confirmed AE. A generalised linear model was used to compare among groups using robust standard errors (SE).

Results

Forty-one AEs were reported in a cohort of 417 patients (234 females), with 30 AEs reported by 3 months. Eleven (27 reported) infections, two (six reported) periprosthetic fractures and two (eight reported) dislocations were confirmed. Those in the no AE group reported significantly better outcomes that the reported AE group as measured by WOMAC Co-Eff 14.27 (p = 0.01), EQ5D − 0.128 (p = 0.02) and SAPS − 9.926 (p = 0.036) and the combined reported and confirmed AE groups as measured by WOMAC Co-Eff 13.72 (p = 0.002), EQ5D − 0.129 (p = 0.036) and SAPS − 11.512 (p = 0.004). No significant differences were seen in WPAI among groups.

Conclusions

Patients who report AEs have worse outcomes than those who do not, regardless of whether the AEs can be confirmed by standard medical record review methods. The observed negative trends suggest that patient perception of AEs may influence patient outcome in a similar way to those with confirmed AEs.
Loosening and revision rates after total shoulder arthroplasty: a systematic review of cemented all-polyethylene glenoid and three modern designs of metal-backed glenoid
Authors: Kim Dong Min , Aldeghaither Mohammed , Alabdullatif Fahad , Shin Myung Jin , Kholinne Erica , Kim Hyojune , Jeon In-Ho , Koh Kyoung-Hwan
Published: February 2020

Background

Several modern designs of metal-backed glenoids (MBG) have been devised to overcome flaws such as loosening and a high failure rate. This review aimed to compare rates of complications and revision surgeries between cemented polyethylene glenoid (PEG) and three examples of modern MBG designs.

Methods

Literature search was carried out using PubMed, Cochrane Library, EMBASE, and Google Scholar using MeSH terms and natural keywords. A total of 1186 articles were screened. We descriptively analyzed numerical data between the groups and statistically analyzed the categorical data, such as the presence of radiolucent line, loosening, and revision surgery (failure). Articles were divided into three groups based on follow-up duration: < 36-month, 36–72-month, and > 72-month subgroups.

Results

This study included 35 articles (3769 shoulders); 25 on cemented PEG and ten on the modern MBG. Mean age was 66.4 (21–93) and 66.5 years (31–88). The mean duration of follow-up was 73.1 (12–211) and 56.1 months (24–100). Overall, the rate of the radiolucent line was 354/1302 (27%) and 47/282 (17%), the loosening rate was 465/3185 (15%) and 22/449 (5%), and the failure rate was 189/3316 (6%) and 11/457 (2%), for PEG and MBG, respectively. The results of < 36-month and 36–72-month subgroups showed lower rates of radiolucency and loosening in the cemented PEG group, but there was no significant difference in failure rate (P = 0.754 and 0.829, respectively). In the > 72-month subgroup, MBG was better in terms of loosening (P < 0.001) and failure rates (P = 0.006).

Conclusions

The modern MBG component, especially TM glenoid, seems to be a promising alternative to cemented PEGs, based on subgroup revision rates according to the follow-up duration and overall results of ROM and clinical scores. All polyethylene glenoids tend to increase loosening and failure over time. Three modern MBG designs seem to have no difference in failure, at least in the < 36-month and 36–72-month subgroups compared to the cemented PEG. More long-term follow-up studies on modern MBG should be ultimately conducted.

Level of evidence

Level IV, systematic review.
Endoscopic treatment of early leaks and strictures after laparoscopic one anastomosis gastric bypass
Authors: Younis Fadi , Shnell Mati , Gluck Nathan , Abu-Abeid Subhi , Eldar Shai , Fishman Sigal
Published: February 2020

Background

Laparoscopic one anastomosis gastric bypass has become a prominent bariatric procedure. Yet, early and late complications, primarily leaks and strictures, are not uncommon. This study summarizes our experience with endoscopic treatment of laparoscopic one anastomosis gastric bypass complications.

Methods

This is a retrospective study of consecutive patients referred to our hospital from 2015 to 2017 with post laparoscopic one anastomosis gastric bypass complications. Therapy was tailored to each case, including fully covered self-expandable metal stents, fibrin glue, septotomy, internal drainage with pigtail stents, through-the-scope and pneumatic dilation. Success was defined as resuming oral nutrition without enteral or parenteral support or further surgical intervention.

Results

Nine patients presented with acute or early leaks: 5 (56%) had staple-line leaks, 3 (33%) had anastomotic leaks and 1 (11%) had both. All were treated with stents. Adjunctive endoscopic drainage was applied in 4 patients (44%). Overall 5 patients (56%) with acute/ early leaks recovered completely, including all 3 patients with anastomotic leak and the patient with both leaks but only 1/5 with staple line leak (20%). Complication rate in the leak group reached 22%. Eight patients presented with strictures, 7 at the anastomosis and one due to remnant stomach misalignment. All anastomotic strictures were dilated successfully. However, the patient with the pouch stricture required conversion to Roux-en-Y gastric bypass after 3 failed attempts of dilation.

Conclusion

Endoscopic treatments of laparoscopic one anastomosis gastric bypass complications are relatively effective and safe. Anastomosis-related complications are more amenable to endoscopic treatment compared to staple line leaks.
Sexual dysfunction in women with multiple sclerosis: prevalence and impact on quality of life
Authors: Nazari Fatemeh , Shaygannejad Vahid , Mohammadi Sichani Mehrdad , Mansourian Marjan , Hajhashemi Valiollah
Published: February 2020

Background

Sexual function is a component of quality of life, and sexual dysfunction entails reduced satisfaction with life and impaired mood and quality of relationships and affects not only the individual’s quality of life, but her partner’s life as well. Since Sexual Dysfunction (SD) is among the most common complaints of patients with Multiple Sclerosis (MS), this study was conducted to determine the prevalence of SD among women with MS and its effect on quality of life.

Materials and methods

This cross-sectional study was conducted in 2018 on 300 women with MS aged 22–50 years in Isfahan, Iran, selected through systematic random sampling. Data were collected using the standard Female Sexual Function Index (FSFI) and MSQOL-54 and analyzed in SPSS using descriptive and analytical statistics.

Results

The overall prevalence of SD was found as 69.8% in women with MS, with the dimension of sexual desire being affected in 38.6% of the cases, sexual arousal in 38.6%, lubrication in 23.7%, orgasm in 37.3%, satisfaction in 23.4% and pain in 16.9%. SD was found to have significant relationships with age, duration of marriage, fatigue, EDSS and the combined physical and mental health aspects of quality of life (P <  0.05). Moreover, logistic regression analysis revealed that there was a higher probability of a sexual dysfunction among patients with MS and a high fatigue score [1.228(1.003 to 1.504); P = 0.047]. The mean score of the combined physical and mental health aspects of quality of life was lower in the group of women with MS and SD compared to those without SD, and the difference between the two groups was statistically significant (P <  0.05).

Conclusion

Sexual dysfunction is highly prevalent among women with MS and affects various dimensions of quality of life. Greater attention should be paid to the sexual problems faced by MS patients in order to improve their quality of life.
Effects of media-assisted therapeutic approaches on physical activity of obese adults: a systematic review
Authors: Ziegeldorf Alexandra , Wagner Petra , Wulff Hagen
Published: February 2020

Background

The number of patients with obesity continues to increase in our society. At the same time, digitalization defines our everyday life. Therefore, the question arises whether to use digital media for effective treatments against obesity. Aim of this review is a concise presentation of effects of media-assisted therapeutic approaches.

Methods

A systematic literature research in multiple scientific databases, PubMed, Web of Science and Cochrane Library, was performed for literature published in the last 10 years (cut-off date 12.07.2017). Only randomized controlled trials using digital support for treatment and/or aftercare of obese adults aged between 18 to 70 years were included into the analysis.

Results

Overall, 14 trials with data on a total of 4979 participants were included in this review. Generally, there are positive trends for increased moderate to vigorous physical activity by the use of digital media. A simultaneous usage of various digital media, which focus on important aspects of activity behavior, has proven to be effective. A combination of various digital media shows the greatest positive effect and could significantly increase physical activity. However, the biggest potential was found in mixed approaches combining digital devices and personal face-to-face support.

Conclusions

Therapeutic approaches using digital media for supporting obesity treatment did not show superior benefit over traditional personal therapeutic methods. Nevertheless, using both methods together offered the greatest potential for successful obesity therapy. However, there is a backlog of transparency concerning information about the content of treatment. Furthermore, there is a lack of valid data about aftercare and follow-up.
Multi-criteria analysis in the health area: selection of the most appropriate triage system for the emergency care units in natal
Authors: Camilo Deyse Gillyane Gomes , de Souza Ricardo Pires , Frazão Talita Dias Chagas , da Costa Junior João Florêncio
Published: February 2020

Background

Multiobjective decision-making processes present a high degree of complexity in their solution, and tools such as multicriteria decision analysis appear as a way to facilitate the decision-makers’ solution and ensure that the decision is made cohesively and efficiently. In the public health sector, decisions are even more delicate because they work not only with the direct influence of human needs, but also with limited financial resources. An important point for the emergency care units is the triage system, which consists of a pre-evaluation of the patients, classifying them according to the degree of life risk. Through triage, the patient can be attended more quickly and efficiently, streamlining the whole process. Thus, the present research endeavored to determine the most appropriate triage protocol for emergency healthcare units in Natal-RN city in Brazil and may help others less advanced countries to determine the most appropriate triage protocol for emergency healthcare.

Methods

In this study, we used the multicriteria analysis method known as FITradeoff. In addition, interviews and structured questionnaires applied with nurses, specialists and directors.

Results

Based on the questionnaires and preferences presented by the decision-makers, the Spanish Triage System was the most suitable protocol for the emergency care units, which presented with high ease of use and implementation.

Conclusions

This study reached its main objective, which was to determine the most appropriate triage protocol. In addition, it was observed the possibility of new research, such as the development of a specific protocol for this emergency care units and the creation of an application software for this new protocol.
Use of real-time multiplex PCR, malaria rapid diagnostic test and microscopy to investigate the prevalence of Plasmodium species among febrile hospital patients in Sierra Leone
Authors: Leski Tomasz A. , Taitt Chris Rowe , Swaray Abdulai G. , Bangura Umaru , Reynolds Nathanael D. , Holtz Andrew , Yasuda Chadwick , Lahai Joseph , Lamin Joseph M. , Baio Victoria , Jacobsen Kathryn H. , Ansumana Rashid , Stenger David A.
Published: February 2020

Background

Malaria continues to affect over 200 million individuals every year, especially children in Africa. Rapid and sensitive detection and identification of Plasmodium parasites is crucial for treating patients and monitoring of control efforts. Compared to traditional diagnostic methods such as microscopy and rapid diagnostic tests (RDTs), DNA based methods, such as polymerase chain reaction (PCR) offer significantly higher sensitivity, definitive discrimination of Plasmodium species, and detection of mixed infections. While PCR is not currently optimized for routine diagnostics, its role in epidemiological studies is increasing as the world moves closer toward regional and eventually global malaria elimination. This study demonstrates the field use of a novel, ambient temperature-stabilized, multiplexed PCR assay in a small hospital setting in Sierra Leone.

Methods

Blood samples from 534 febrile individuals reporting to a hospital in Bo, Sierra Leone, were tested using three methods: a commercial RDT, microscopy, and a Multiplex Malaria Sample Ready (MMSR) PCR designed to detect a universal malaria marker and species-specific markers for Plasmodium falciparum and Plasmodium vivax. A separate PCR assay was used to identify species of Plasmodium in samples in which MMSR detected malaria, but was unable to identify the species.

Results

MMSR detected the presence of any malaria marker in 50.2% of all tested samples with P. falciparum identified in 48.7% of the samples. Plasmodium vivax was not detected. Testing of MMSR P. falciparum-negative/universal malaria-positive specimens with a panel of species-specific PCRs revealed the presence of Plasmodium malariae (n = 2) and Plasmodium ovale (n = 2). The commercial RDT detected P. falciparum in 24.6% of all samples while microscopy was able to detect malaria in 12.8% of tested specimens.

Conclusions

Wider application of PCR for detection of malaria parasites may help to fill gaps existing as a result of use of microscopy and RDTs. Due to its high sensitivity and specificity, species coverage, room temperature stability and relative low complexity, the MMSR assay may be useful for detection of malaria and epidemiological studies especially in low-resource settings.
Clinical and laboratory features associated with serum phosphate concentrations in malaria and other febrile illnesses
Authors: Suen Ho-Ming E. , Pasvol Geoffrey , Cunnington Aubrey J.
Published: February 2020

Background

Hypophosphatemia is common in severe infections including malaria. Previous studies suggested that serum phosphate concentrations correlate with temperature, but it is unclear whether the type of infection and other factors occurring during infection influence this association. Here relationships were investigated between serum phosphate levels, cause of fever, demographic, clinical and laboratory parameters.

Methods

Anonymized data were analysed from 633 adults with malaria or other febrile illness admitted to Northwick Park Hospital, London, UK. Univariable and multivariable generalized linear model analyses were performed to examine associations with serum phosphate levels. Interaction terms were included to investigate whether cause of fever (malaria vs other illness), malaria parasite species, or malaria severity influenced the association of other variables with phosphate.

Results

Hypophosphatemia was common in subjects with malaria (211/542 (39%)), and in other febrile illnesses (24/91 (26%)), however median phosphate levels did not differ significantly by diagnostic group, parasite species or severity of malaria. In all analyses, there were highly significant negative associations between serum phosphate and axillary temperature, and positive associations between serum phosphate and platelet count. There were no significant interactions between these variables and cause of fever, parasite species or severity of illness. Sodium and potassium concentrations were associated with serum phosphate in subjects with malaria and when data from all subjects was combined.

Conclusion

Serum phosphate is consistently associated with temperature and platelet count in adults with diverse causes of fever. This may be a consequence of phosphate shifts from plasma into cells to support ATP generation for thermogenesis and platelet activation.
Acromegaly with congenital generalized lipodystrophy – two rare insulin resistance conditions in one patient: a case report
Authors: Guerreiro Vanessa , Bernardes Irene , Pereira Josué , Silva Roberto Pestana , Fernandes Susana , Carvalho Davide , Freitas Paula
Published: February 2020

Background

Lipodystrophies are a group of diseases which are characterized by abnormal adipose tissue deposition and are frequently associated with metabolic changes. Congenital generalized lipodystrophy is an autosomal recessive syndrome, with a prevalence < 1:10 million. Acromegaly is a rare disease, secondary to the chronic hypersecretion of growth hormone and insulin-like growth factor-1, with characteristic metabolic and somatic effects. “Acromegaloidism” is a term used for patients who manifest clinical features of acromegaly, but do not present a demonstrable hormone growth hypersecretion. The extreme shortage of subcutaneous adipose tissues and muscle hypertrophy confer an acromegaloid-like appearance in these patients.

Case presentation

We describe a case of a patient with the rare combination of Berardinelli–Seip congenital lipodystrophy and acromegaly; our patient is a 63-year-old white man, who was referred to an endocrinology consultation for suspected lipodystrophy. He had lipoatrophy of upper and lower limbs, trunk, and buttocks, with muscular prominence, acromegaloid facial appearance, large extremities, and soft tissue tumescence. In addition, he had dyslipidemia and prediabetes. His fat mass ratio (% trunk fat mass/% lower limbs fat mass) was 1.02 by densitometry and he also had hepatomegaly, with mild steatosis (from an abdominal ultrasound), and left ventricular hypertrophy (from an electrocardiogram). His first oral glucose tolerance test had growth hormone nadir of 0.92 ng/mL, and the second test, 10 months afterwards, registered growth hormone nadir of 0.64 ng/mL (growth hormone nadir < 0.3 ng/mL excludes acromegaly). Pituitary magnetic resonance imaging identified an area of hypocaptation of contrast product in relation to a pituitary adenoma and he was subsequently submitted to transsphenoidal surgical resection of the mass. A pathological evaluation showed pituitary adenoma with extensive expression of growth hormone and adrenocorticotropic hormone, as well as a rare expression of follicle-stimulating hormone and prolactin.

A genetic study revealed an exon 3/exon 4 deletion of the AGPAT2 gene in homozygosity.

Conclusions

Congenital generalized lipodystrophy is a rare disease which occurs with acromegaloid features. As far as we know, we have described the first case of genetic lipodystrophy associated with true acromegaly.

Although this is a rare association, the presence of congenital generalized lipodystrophy should not exclude the possibility of simultaneous acromegaly.
Effects of SW033291 on the myogenesis of muscle-derived stem cells and muscle regeneration
Authors: Dong Yuanqiang , Li Yuan , Zhang Chuan , Chen Haibin , Liu Lijia , Chen Simeng
Published: February 2020

Background

The unmet medical needs in repairing large muscle defects promote the development of tissue regeneration strategy. The use of bioactive molecules in combination with biomaterial scaffold has become an area of great interest. SW033291, a small-molecule inhibitor targeting 15-hydroxyprostaglandin dehydrogenase (15-PDGH) and subsequently elevating the production of prostaglandin E2 (PGE2), has been proved to accelerate the recovery and potentiate the regeneration of multiple tissues including the bone, liver, and colon. The limited understanding of the potential therapeutic effects on myogenesis motivated us to investigate the role of SW033291 in regulating muscle-derived stem cell (MDSC) myogenic differentiation and MDSC-mediated muscle regeneration.

Methods

The characteristics of rat MDSCs, including cell-specific markers and myogenic differentiation potential, were determined. MDSCs were incubated with SW033291 to evaluate PGE2 production and cytotoxicity. The effects of SW033291 on MDSC myogenic differentiation were assessed by quantitative real-time polymerase chain reaction (qPCR), western blot, and immunocytochemistry. The fibrin gel containing MDSCs and SW033291 was used for muscle regeneration in a tibialis anterior muscle defect model.

Results

Our data demonstrated that MDSCs were well-tolerated to SW033291 and treatment with SW033291 significantly promoted the production of PGE2 by MDSCs. In vitro analysis showed that SW033291 enhanced the myogenic differentiation and myotube formation by upregulating a series of myogenic markers. Additionally, the activation of PI3K/Akt pathway was involved in the mechanism underlying these promotive effects. Then, in situ casting of fibrin gel containing MDSCs and SW033291 was used to repair the tibialis anterior muscle defect; the addition of SW033291 significantly promoted myofiber formation within the defect region with mild immune response, less fibrosis, and sufficient vascularization.

Conclusion

SW033291 acted as a positive regulator of MDSC myogenic differentiation, and incorporating the compound with MDSCs in fibrin gel could serve as an effective method to repair large skeletal muscle defects.
Vasomotor Symptoms and Accelerated Epigenetic Aging in the Women’s Health Initiative (WHI)
Authors: Thurston Rebecca C , Carroll Judith E , Levine Morgan , Chang Yuefang , Crandall Carolyn , Manson JoAnn E , Pal Lubna , Hou Lifang , Shadyab Aladdin H , Horvath Steve
Published: February 2020

Purpose

The hallmark menopausal symptom, vasomotor symptoms (VMS), has been linked to adverse health indicators. However, the relationship between VMS and biological aging has not been tested. We examined associations between menopausal VMS and biological aging as assessed by 2 DNA methylation-based epigenetic aging indicators previously linked to poor health outcomes.

Methods

Participants were members of the Women’s Health Initiative Observational Study integrative genomics substudy (N = 1206) who had both ovaries and were not taking hormone therapy. Relationships between VMS at enrollment (presence, severity) or VMS timing groups (no VMS: not at menopause onset nor at study enrollment; early VMS: at menopause onset but not at enrollment; persistent VMS: at menopause onset and study enrollment; and late VMS: at enrollment but not at menopause onset) and epigenetic clock indicators predictive of physical aging and early death (DNAm PhenoAge, DNAm GrimAge) were tested in linear regression models adjusting for age, race/ethnicity, hysterectomy, education, body mass index, smoking, and, in additional models, sleep disturbance.

Results

Women were on average 65 years of age at enrollment. Severe hot flashes at enrollment were associated with higher DNAm PhenoAge [relative to no hot flashes: B (SE) = 2.79 (1.27), P = 0.028, multivariable]. Further, late-occurring VMS were associated with both higher DNAm PhenoAge [B (SE) = 2.15 (0.84), P = 0.011] and DNAm GrimAge [B (SE) = 1.09 (0.42), P = 0.010, multivariable] relative to no VMS.

Main Conclusions

Among postmenopausal women, severe or late-occurring VMS were associated with accelerated epigenetic age, controlling for chronological age. Postmenopausal women with severe or late-occurring VMS may have greater underlying epigenetic aging.
Youth Metabolic Equivalents Differ Depending on Operational Definitions
Authors: HIBBING PAUL R. , BASSETT DAVID R. , COE DAWN P. , LAMUNION SAMUEL R. , CROUTER SCOTT E.
Published: February 2020

Youth metabolic equivalents (METy) are sometimes operationally defined as multiples of predicted basal metabolic rate (METyBMR) and other times as multiples of measured resting metabolic rate (METyRMR).

Purpose

This study aimed to examine the comparability of METyBMR and METyRMR.

Methods

Indirect calorimetry data (Cosmed K4b2) were analyzed from two studies, with a total sample of 245 youth (125 male participants, 6–18 yr old, 37.4% overweight or obese). The Schofield equations were used to predict BMR, and K4b2 data from 30 min of supine rest were used to assess RMR. Participants performed structured physical activities (PA) of various intensities, and steady-state oxygen consumption was divided by predicted BMR and measured RMR to calculate METyBMR and METyRMR, respectively. Two-way (activity–METy calculation) analysis of variance was used to compare METyBMR and METyRMR (α = 0.05), with Bonferroni-corrected post hoc tests. Intensity classifications were also compared after encoding METyBMR and METyRMR as sedentary behavior (≤1.50 METy), light PA (1.51–2.99 METy), moderate PA (3.00–5.99 METy), or vigorous PA (≥6.00 METy).

Results

There was a significant interaction (F(30) = 3.6, P < 0.001), and METyBMR was significantly higher than METyRMR for 28 of 31 activities (P < 0.04), by 15.6% (watching television) to 23.1% (basketball). Intensity classifications were the same for both METy calculations in 69.0% of cases.

Conclusions

METyBMR and METyRMR differ considerably. Greater consensus is needed regarding how metabolic equivalents should be operationally defined in youth, and in the meantime, careful distinction is necessary between METyBMR and METyRMR.
Fatigue and Recovery after Single-Stage versus Multistage Ultramarathon Running
Authors: BESSON THIBAULT , ROSSI JÉRÉMY , LE ROUX MALLOUF THIBAULT , MARECHAL MATTHIEU , DOUTRELEAU STÉPHANE , VERGES SAMUEL , MILLET GUILLAUME Y.
Published: February 2020

Purpose

Ultramarathon running includes two main types of events: single-stage race (SSR) and multistage races (MSR). Direct comparison of neuromuscular fatigue and recovery after SSR versus MSR race of comparable distance and elevation has never been performed. The aim of this study was to assess neuromuscular fatigue and recovery after two ultramarathons of equal distance performed either (i) in a single stage or (ii) in four successive days.

Methods

Thirty-one runners participated in the study: 17 ran 169 km in a single-stage race and 14 performed around 40 km·d−1 over 4 d. The two races were performed on the same course. Neuromuscular function was tested before (PRE), after (POST), and 2 (D + 2), 5 (D + 5) and 10 (D + 10) days after the races. Neuromuscular function was evaluated on both knee extensors (KE) and plantar flexors (PF) with voluntary and evoked contractions using electrical (femoral and tibial, respectively) nerve stimulation.

Results

Reduction of voluntary activation measured in the KE was greater (i.e., central fatigue) for SSR than MSR directly after the race (−23% vs −7%), P < 0.01). Reductions in evoked mechanical KE and PF responses on relaxed muscle (i.e., peripheral fatigue) of both KE and PF took longer to recover in MSR than in SSR.

Conclusions

Performing prolonged running exercise over several days, each separated by rest, elicits more prolonged impairments in contractile function compared with single-stage ultramarathon, whereas single-stage mountain ultramarathon ran on the same course is associated with greater central fatigue.
Η δύναμη της κινούμενης εικόνας και του εκπαιδευτικού βίντεο στην προώθηση της μάθησης
Authors: Γεωργαντα Bικυ Eυάγγελος
Published: February 2020

Είναι αδιαμφισβήτητο γεγονός ότι η παιδεία αποτελεί βασικό συστατικό µιας πολιτισµένης κοινωνίας, ως προϋπόθεση και εγγύηση τόσο της συνέχειάς της όσο και της καινοτομίας της. Η σημασία τόσο της γενικής παιδείας όσο και της υψηλής ποιότητας εκπαίδευσης αφορά όλα τα γνωστικά αντικείμενα. Η ανάγκη για την καλλιέργεια της ικανότητας της ανάγνωσης και της αξιολόγησης των οπτικών μηνυμάτων προβάλει επιτακτικά στη σύγχρονη συγκυρία στο βαθμό που η εικόνα διαδραματίζει καθοριστικό ρόλο στο σύγχρονο επικοινωνιακό και κοινωνικό περιβάλλον. Tο σχολείο, ως φορέας αγωγής, καλείται να προσφέρει στους εκπαιδευόμενους τα αναγκαία εφόδια, ώστε να είναι σε θέση να κατανοούν και να χρησιμοποιούν τον αντίστοιχο κώδικα επικοινωνίας. Η κυριαρχία των εικόνων και η χρήση πολυτροπικών κωδικών επικοινωνίας προβάλλουν επιτακτικά την ανάγκη για παροχή οπτικοακουστικής παιδείας, στο πλαίσιο του πολυγραμματισμού, η οποία θα στοχεύει στην εξοικείωση των παιδιών μέσα στο σχολείο με κώδικες και μεθόδους, ώστε να εξοπλίζονται με εργαλεία κριτικής αντιμετώπισης των εκπεμπόμενων μηνυμάτων είτε αυτά είναι γραπτά, είτε οπτικά ή ηχητικά. Η εξοικείωση με τις εκφραστικές δυνατότητες των οπτικοακουστικών τεχνών περιλαμβάνει όχι μόνο την προσέγγιση και γνωριμία των παιδιών με χαρακτηριστικά έργα, αλλά και τη δυνατότητα των παιδιών να παράγουν τα δικά τους έργα. Στόχος θα πρέπει να είναι η ενσωμάτωση προγραμμάτων οπτικοακουστικού γραμματισμού στα προγράμματα σπουδών και η ανάπτυξη δραστηριοτήτων στα γνωστικά αντικείμενα του ελληνικού σχολείου. Από την άλλη πλευρά το εκπαιδευτικό βίντεο, όταν είναι κατάλληλα σχεδιασμένο μπορεί να ενεργοποιήσει μια σειρά από μηχανισμούς μάθησης και να αποτελέσει σημαντικό εκπαιδευτικό εργαλείο.