bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved clinical outcomes of preimplantation genetic testing for aneuploidy using MALBAC-NGS compared with MDA-SNP array
Authors: Niu Wenbin , Wang Linlin , Xu Jiawei , Li Ying , Shi Hao , Li Gang , Jin Haixia , Song Wenyan , Wang Fang , Sun Yingpu
Published: July 2020

Background

To assess whether preimplantation genetic testing for aneuploidy with next generation sequencing (NGS) outweighs single nucleotide polymorphism (SNP) array in improving clinical outcomes.

Methods

A retrospective analysis of the clinical outcomes of patients who underwent PGT-A treatment in a single center from January 2013 to December 2017.A total of 1418 couples who underwent PGT-A treatment were enrolled, of which 805 couples used NGS for PGT-A, while the remaining 613 couples used SNP array for PGT-A. Clinical pregnancy rate, miscarriage rate and healthy baby rate were compared between the MALBAC-NGS-PGT-A and MDA-SNP-PGT-A groups.

Results

After testing karyotypes of 5771 biopsied blastocysts, 32.2% (1861/5771) were identified as chromosomally normal, while 67.8% were chromosomally abnormal. In terms of clinical outcomes, women in the MALBAC-NGS-PGT-A group had a significantly higher clinical pregnancy rate (50.5% vs 41.7%, p = 0.002) and healthy baby rate (39.6% vs 31.4%, p = 0.003), and a lower miscarriage rate (15.5% vs 22.8%, p = 0.036).

Conclusion

This is the largest study reporting the extensive application of NGS-based PGT-A, whilst comparing the clinical outcomes of MALBAC-NGS-PGT-A and MDA-SNP-PGT-A. The results provide greater evidence supporting the wider use of NGS in PGT-A, not only for its lower cost but also for its improved clinical outcomes compared to SNP-based PGT-A.
Design and methods of a national, multicenter, randomized and controlled trial to assess the efficacy of a physical activity program to improve health-related quality of life and reduce fatigue in women with metastatic breast cancer: ABLE02 trial
Authors: Delrieu Lidia , Anota Amélie , Trédan Olivier , Freyssenet Damien , Maire Aurélia , Canada Brice , Fournier Baptiste , Febvey-Combes Olivia , Pilleul Frank , Bouhamama Amine , Caux Christophe , Joly Florence , Fervers Béatrice , Pialoux Vincent , Pérol David , Pérol Olivia
Published: July 2020

Background

Patients with a metastatic breast cancer suffer from a deteriorated health-related quality of life and numerous symptoms such as pain, severe fatigue and a decrease of their physical fitness. As the feasibility of a physical activity program has been demonstrated in this population, ABLE02 aims to assess the efficacy of a 6 month-physical activity program using connected devices to improve health-related quality of life and to reduce fatigue in women with metastatic breast cancer.

Methods

ABLE02 is a prospective, national, multicenter, randomized, controlled and open-label study. A total of 244 patients with a metastatic breast cancer, with at least one positive hormone receptor and a first-line chemotherapy planned, will be randomly assigned (1:1 ratio) to: (i) the intervention arm to receive physical activity recommendations, an activity tracker to wear 24 h a day during the whole intervention (6 months) with at least three weekly walking sessions and quizzes each week on physical activity and nutrition (ii) the control arm to receive physical activity recommendations only. Health-related quality of life will be assessed every 6 weeks and main assessments will be conducted at baseline, M3, M6, M12 and M18 to evaluate the clinical, physical, biological and psychological parameters and survival of participants. All questionnaires will be completed on a dedicated application.

Discussion

An activity program based on a smartphone application linked to an activity tracker may help to improve quality of life and reduce fatigue of patients with a metastatic breast cancer. The growth of e-health offers the opportunity to get real-time data as well as improving patient empowerment in order to change long-term behaviors.

Trial registration

NCT number: NCT04354233.
Access to sexual and reproductive health commodities in East and Southern Africa: a cross-country comparison of availability, affordability and stock-outs in Kenya, Tanzania, Uganda and Zambia
Authors: Ooms Gaby I. , Kibira Denis , Reed Tim , van den Ham Hendrika A. , Mantel-Teeuwisse Aukje K. , Buckland-Merrett Gemma
Published: July 2020

Background

Access to sexual and reproductive health services continues to be a public health concern in Kenya, Tanzania, Uganda and Zambia: use of modern contraceptives is low, and unmet family planning needs and maternal mortality remain high. This study is an assessment of the availability, affordability and stock-outs of essential sexual and reproductive health commodities (SRHC) in these countries to inform interventions to improve access.

Methods

The study consisted of an adaptation of the World Health Organization/Health Action International methodology,Measuring Medicine Prices, Availability, Affordability and Price Components. Price, availability and stock-out data was collected in July 2019 for over fifty lowest-priced SRHC from public, private and private not-for-profit health facilities in Kenya (n = 221), Tanzania (n = 373), Uganda (n = 146) and Zambia (n = 245). Affordability was calculated using the wage of a lowest-paid government worker. Accessibility was illustrated by combining the availability (≥ 80%) and affordability (less than 1 day’s wage) measures.

Results

Overall availability of SRHC was low at less than 50% in all sectors, areas and countries, with highest mean availability found in Kenyan public facilities (46.6%). Stock-outs were common; the average number of stock-out days per month ranged from 3 days in Kenya’s private and private not-for-profit sectors, to 12 days in Zambia’s public sector. In the public sectors of Kenya, Uganda and Zambia, as well as in Zambia’s private not-for-profit sector, all SRHC were free for the patient. In the other sectors unaffordability ranged from 2 to 9 SRHC being unaffordable, with magnesium sulphate being especially unaffordable in the countries. Accessibility was low across the countries, with Kenya’s and Zambia’s public sectors having six SRHC that met the accessibility threshold, while the private sector of Uganda had only one SRHC meeting the threshold.

Conclusions

Accessibility of SRHC remains a challenge. Low availability of SRHC in the public sector is compounded by regular stock-outs, forcing patients to seek care in other sectors where there are availability and affordability challenges. Health system strengthening is needed to ensure access, and these findings should be used by national governments to identify the gaps and shortcomings in their supply chains.
Deformity progression in congenital posteromedial bowing of the tibia: a report of 44 cases
Authors: Di Gennaro Giovanni Luigi , Gallone Giovanni , Martinez Vazquez Edgar Alejandro , Marchesini Reggiani Leonardo , Racano Costantina , Olivotto Eleonora , Stilli Stefano , Trisolino Giovanni
Published: July 2020

Background

congenital posteromedial bowing of tibia (CPMBT) is a very rare birth defect, characterized by shortened bowed leg and ankle deformity. We described a single institution experience in the management of CPMBT.

Methods

we identified 44 CPMBT in 44 children. The age at presentation was 5.5 ± 5.6 years and the mean age at the final review was 10.1 ± 4.8 years. Radiographic evaluation included the antero-posterior and lateral inter-physeal angle (AP-IPA and L-IPA), the limb length discrepancy (LLD), the morphology of the distal tibia and the lateral distal tibial angle (LDTA). During the study period, 26 children underwent surgical treatment.

Results

the estimated curves showed a progressive spontaneous correction of both AP-IPA and L-IPA during growth, but a progressive increase of the LLD. The L-IPA showed a more predictable behaviour while the AP-IPA showed a scattered correction, with a wider variation of the estimated final angle. The final LDTA was 85.3° ± 4.2° and was correlated with the L-IPA (r = 0.5; p = 0.02).

Among the 26 children who underwent surgical treatment, 23 cases had limb lengthening, 1 case had contralateral epiphysiodesis, 1 child underwent tibial osteotomy, 1 patient was treated by hemiepiphysiodesis of the distal tibia to correct ankle valgus deformity.

Conclusions

our study described the largest case series of CPMBT. A combination of surgical treatments, in a staged surgical process, should be tailored to the developmental characteristics of this abnormality. An experience-based algorithm of treatment is also proposed. Further studies are needed to understand which is the best strategy to correct this deformity during childhood.

Level of evidence

level IV prognostic study.
A risk calculator to inform the need for a prostate biopsy: a rapid access clinic cohort
Authors: Jalali Amirhossein , Foley Robert W. , Maweni Robert M. , Murphy Keefe , Lundon Dara J. , Lynch Thomas , Power Richard , O’Brien Frank , O’Malley Kieran J. , Galvin David J. , Durkan Garrett C. , Murphy T. Brendan , Watson R. William
Published: July 2020

Background

Prostate cancer (PCa) represents a significant healthcare problem. The critical clinical question is the need for a biopsy. Accurate risk stratification of patients before a biopsy can allow for individualised risk stratification thus improving clinical decision making. This study aims to build a risk calculator to inform the need for a prostate biopsy.

Methods

Using the clinical information of 4801 patients an Irish Prostate Cancer Risk Calculator (IPRC) for diagnosis of PCa and high grade (Gleason ≥7) was created using a binary regression model including age, digital rectal examination, family history of PCa, negative prior biopsy and Prostate-specific antigen (PSA) level as risk factors. The discrimination ability of the risk calculator is internally validated using cross validation to reduce overfitting, and its performance compared with PSA and the American risk calculator (PCPT), Prostate Biopsy Collaborative Group (PBCG) and European risk calculator (ERSPC) using various performance outcome summaries. In a subgroup of 2970 patients, prostate volume was included. Separate risk calculators including the prostate volume (IPRCv) for the diagnosis of PCa (and high-grade PCa) was created.

Results

IPRC area under the curve (AUC) for the prediction of PCa and high-grade PCa was 0.6741 (95% CI, 0.6591 to 0.6890) and 0.7214 (95% CI, 0.7018 to 0.7409) respectively. This significantly outperforms the predictive ability of cancer detection for PSA (0.5948), PCPT (0.6304), PBCG (0.6528) and ERSPC (0.6502) risk calculators; and also, for detecting high-grade cancer for PSA (0.6623) and PCPT (0.6804) but there was no significant improvement for PBCG (0.7185) and ERSPC (0.7140). The inclusion of prostate volume into the risk calculator significantly improved the AUC for cancer detection (AUC = 0.7298; 95% CI, 0.7119 to 0.7478), but not for high-grade cancer (AUC = 0.7256; 95% CI, 0.7017 to 0.7495). The risk calculator also demonstrated an increased net benefit on decision curve analysis.

Conclusion

The risk calculator developed has advantages over prior risk stratification of prostate cancer patients before the biopsy. It will reduce the number of men requiring a biopsy and their exposure to its side effects. The interactive tools developed are beneficial to translate the risk calculator into practice and allows for clarity in the clinical recommendations.
The impact of PD-L1 N-linked glycosylation on cancer therapy and clinical diagnosis
Authors: Wang Ying-Nai , Lee Heng-Huan , Hsu Jennifer L. , Yu Dihua , Hung Mien-Chie
Published: July 2020

N-linked glycosylation is one of the most abundant posttranslational modifications of membrane-bound proteins in eukaryotes and affects a number of biological activities, including protein biosynthesis, protein stability, intracellular trafficking, subcellular localization, and ligand-receptor interaction. Accumulating evidence indicates that cell membrane immune checkpoint proteins, such as programmed death-ligand 1 (PD-L1), are glycosylated with heavy N-linked glycan moieties in human cancers. N-linked glycosylation of PD-L1 maintains its protein stability and interaction with its cognate receptor, programmed cell death protein 1 (PD-1), and this in turn promotes evasion of T-cell immunity. Studies have suggested targeting PD-L1 glycosylation as a therapeutic option by rational combination of cancer immunotherapies. Interestingly, structural hindrance by N-glycan on PD-L1 in fixed samples impedes its recognition by PD-L1 diagnostic antibodies. Notably, the removal of N-linked glycosylation enhances PD-L1 detection in a variety of bioassays and more accurately predicts the therapeutic efficacy of PD-1/PD-L1 inhibitors, suggesting an important clinical implication of PD-L1 N-linked glycosylation. A detailed understanding of the regulatory mechanisms, cellular functions, and diagnostic limits underlying PD-L1 N-linked glycosylation could shed new light on the clinical development of immune checkpoint inhibitors for cancer treatment and deepen our knowledge of biomarkers to identify patients who would benefit the most from immunotherapy. In this review, we highlight the effects of protein glycosylation on cancer immunotherapy using N-linked glycosylation of PD-L1 as an example. In addition, we consider the potential impacts of PD-L1 N-linked glycosylation on clinical diagnosis. The notion of utilizing the deglycosylated form of PD-L1 as a predictive biomarker to guide anti-PD-1/PD-L1 immunotherapy is also discussed.
Ambient particulate matter and biomass burning: an ecological time series study of respiratory and cardiovascular hospital visits in northern Thailand
Authors: Mueller W. , Loh M. , Vardoulakis S. , Johnston H. J. , Steinle S. , Precha N. , Kliengchuay W. , Tantrakarnapa K. , Cherrie J. W.
Published: July 2020

Background

Exposure to particulate matter (PM) emitted from biomass burning is an increasing concern, particularly in Southeast Asia. It is not yet clear how the source of PM influences the risk of an adverse health outcome. The objective of this study was to quantify and compare health risks of PM from biomass burning and non-biomass burning sources in northern Thailand.

Methods

We collected ambient air pollutant data (PM with a diameter of < 10 μm [PM10], PM2.5, Carbon Monoxide [CO], Ozone [O3], and Nitrogen Dioxide [NO2]) from ground-based monitors and daily outpatient hospital visits in Thailand during 2014–2017. Outpatient data included chronic lower respiratory disease (CLRD), ischaemic heart disease (IHD), and cerebrovascular disease (CBVD). We performed an ecological time series analysis to evaluate the association between daily air pollutants and outpatient visits. We used the 90th and 95th percentiles of PM10 concentrations to determine days of exposure to PM predominantly from biomass burning.

Results

There was significant intra annual variation in PM10 levels, with the highest concentrations occurring during March, coinciding with peak biomass burning. Incidence Rate Ratios (IRRs) between daily PM10 and outpatient visits were elevated most on the same day as exposure for CLRD = 1.020 (95% CI: 1.012 to 1.028) and CBVD = 1.020 (95% CI: 1.004 to 1.035), with no association with IHD = 0.994 (95% CI: 0.974 to 1.014). Adjusting for CO tended to increase effect estimates. We did not find evidence of an exposure response relationship with levels of PM10 on days of biomass burning.

Conclusions

We found same-day exposures of PM10 to be associated with certain respiratory and cardiovascular outpatient visits. We advise implementing measures to reduce population exposures to PM wherever possible, and to improve understanding of health effects associated with burning specific types of biomass in areas where such large-scale activities occur.
Beneficial effects of omega-3 fatty acid supplementation in schizophrenia: possible mechanisms
Authors: Hsu Mei-Chi , Huang Yung-Sheng , Ouyang Wen-Chen
Published: July 2020

Background

Schizophrenia is a serious long-term psychotic disorder marked by positive and negative symptoms, severe behavioral problems and cognitive function deficits. The cause of this disorder is not completely clear, but is suggested to be multifactorial, involving both inherited and environmental factors. Since human brain regulates all behaviour, studies have focused on identifying changes in neurobiology and biochemistry of brain in schizophrenia. Brain is the most lipid rich organ (approximately 50% of brain dry weight). Total brain lipids is constituted of more than 60% of phospholipids, in which docosahexaenoic acid (DHA, 22:6n-3) is the most abundant (more than 40%) polyunsaturated fatty acid (PUFA) in brain membrane phospholipids. Results from numerous studies have shown significant decreases of PUFAs, in particular, DHA in peripheral blood (plasma and erythrocyte membranes) as well as brain of schizophrenia patients at different developmental phases of the disorder. PUFA deficiency has been associated to psychotic symptoms and cognitive deficits in schizophrenia. These findings have led to a number of clinical trials examining whether dietary omega-3 fatty acid supplementation could improve the course of illness in patients with schizophrenia. Results are inconsistent. Some report beneficial whereas others show not effective. The discrepancy can be attributed to the heterogeneity of patient population.

Methods

In this review, results from recent experimental and clinical studies, which focus on illustrating the role of PUFAs in the development of schizophrenia were examined. The rationale why omega-3 supplementation was beneficial on symptoms (presented by subscales of the positive and negative symptom scale (PANSS), and cognitive functions in certain patients but not others was reviewed. The potential mechanisms underlying the beneficial effects were discussed.

Results

Omega-3 fatty acid supplementation reduced the conversion rate to psychosis and improved both positive and negative symptoms and global functions in adolescents at ultra-high risk for psychosis. Omega-3 fatty acid supplementation could also improve negative symptoms and global functions in the first-episode patients with schizophrenia, but improve mainly total or general PANSS subscales in chronic patients. Patients with low PUFA (particularly DHA) baseline in blood were more responsive to the omega-3 fatty acid intervention.

Conclusion

Omega-3 supplementation is more effective in reducing psychotic symptom severity in young adults or adolescents in the prodromal phase of schizophrenia who have low omega-3 baseline. Omega-3 supplementation was more effective in patients with low PUFA baseline. It suggests that patients with predefined lipid levels might benefit from lipid treatments, but more controlled clinical trials are warranted.
Clustering effects of health risk behavior on mental health and physical activity in Chinese adolescents
Authors: Yi Xiangren , Liu Zongyu , Qiao Wenzhen , Xie Xiuye , Yi Nuo , Dong Xiaosheng , Wang Baozhen
Published: July 2020

Purpose

Risk behaviors are significantly impacting physical and psychological health among adolescents, resulting in a tremendous public health issue. The aim of this study is to examine the association of clustered risk behaviors with mental health and physical activity, and identify to what extent the clustering of various risk behaviors is associated with psychological health and physical activity in Chinese adolescents.

Methods

Students aged 16–18 years, male 16.2 ± 1.03, female 16.3 ± 1.56, were recruited from 30 high schools to complete an online questionnaire in fall semester 2017. A structured questionnaire, 2017 state and local youth risk behavior survey was revised, modified, and translated into Chinese. Five questions were designed to assess physical activity times of the last 7 days. Symptom checklist 90 (SCL-90) was used to investigate the mental health status of the participants. Statistical analyses were done employing chi-square tests, two step cluster analysis, logistic regression.

Result

Results illustrate that girls report a significantly higher mean of being bullied in school, electronically bullied, feeling sad or hopeless, and trying cigarette smoking. Two-step cluster analysis and regression analysis find that alcohol use, smoking and sedentary behavior have significant effect on adolescent health. Logic regression demonstrated that risk behaviors have significantly associated with mental health and physical activity in specific cluster.

Conclusion

This study finds that a specific behavior cluster has significant impact on mental health and physical activity among adolescents. Integrating risk behaviors cluster with factors can be employed to target high-risk adolescents who have poor physical and psychosocial health. The research suggest that more effective and feasible school intervention programs can be designed to promote adolescent health-related behavior in terms of those pathways.
Recommendations for core critical care ultrasound competencies as a part of specialist training in multidisciplinary intensive care: a framework proposed by the European Society of Intensive Care Medicine (ESICM)
Authors: Wong Adrian , Galarza Laura , Forni Lui , De Backer Daniel , Slama Michael , Cholley Bernard , Mayo Paul , McLean Anthony , Vieillard-Baron Antoine , Lichtenstein Daniel , Volpicelli Giovanni , Arntfield Robert , Martin-Loeches Ignacio , Istrate Gizella Melania , Duška František ,   on behalf of ESICM Critical Care Ultrasound Group, Wong Adrian , Galarza Laura , Forni Lui , De Backer Daniel , Slama Michael , Cholley Bernard , Mayo Paul , McLean Anthony , Vieillard-Baron Antoine , Lichtenstein Daniel , Volpicelli Giovanni , Arntfield Robert , Martin-Loeches Ignacio , Istrate Gizella Melania , Duška František
Published: July 2020

Critical care ultrasound (CCUS) is an essential component of intensive care practice. Although existing international guidelines have focused on training principles and determining competency in CCUS, few countries have managed to operationalize this guidance into an accessible, well-structured programme for clinicians training in multidisciplinary intensive care. We seek to update and reaffirm appropriate CCUS scope so that it may be integrated into the international Competency-based Training in Intensive Care Medicine. The resulting recommendations offer the most contemporary and evolved set of core CCUS competencies for an intensive care clinician yet described. Importantly, we discuss the rationale for inclusion but also exclusion of competencies listed.

Background/aim

Critical care ultrasound (CCUS) is an essential component of intensive care practice. The purpose of this consensus document is to determine those CCUS competencies that should be a mandatory part of training in multidisciplinary intensive care.

Methods

A three-round Delphi method followed by face-to-face meeting among 32 CCUS experts nominated by the European Society of Intensive Care Medicine. Agreement of at least 90% of experts was needed in order to enlist a competency as mandatory.

Results

The final list of competencies includes 15 echocardiographic, 5 thoracic, 4 abdominal, deep vein thrombosis diagnosis and central venous access aid.

Conclusion

The resulting recommendations offer the most contemporary and evolved set of core CCUS competencies for an intensive care clinician yet described.
High-resolution temporal profiling of the human gut microbiome reveals consistent and cascading alterations in response to dietary glycans
Authors: Creswell Richard , Tan Jie , Leff Jonathan W. , Brooks Brandon , Mahowald Michael A. , Thieroff-Ekerdt Ruth , Gerber Georg K.
Published: July 2020

Background

Dietary glycans, widely used as food ingredients and not directly digested by humans, are of intense interest for their beneficial roles in human health through shaping the microbiome. Characterizing the consistency and temporal responses of the gut microbiome to glycans is critical for rationally developing and deploying these compounds as therapeutics.

Methods

We investigated the effect of two chemically distinct glycans (fructooligosaccharides and polydextrose) through three clinical studies conducted with 80 healthy volunteers. Stool samples, collected at dense temporal resolution (~ 4 times per week over 10 weeks) and analyzed using shotgun metagenomic sequencing, enabled detailed characterization of participants’ microbiomes. For analyzing the microbiome time-series data, we developed MC-TIMME2 (Microbial Counts Trajectories Infinite Mixture Model Engine 2.0), a purpose-built computational tool based on nonparametric Bayesian methods that infer temporal patterns induced by perturbations and groups of microbes sharing these patterns.

Results

Overall microbiome structure as well as individual taxa showed rapid, consistent, and durable alterations across participants, regardless of compound dose or the order in which glycans were consumed. Significant changes also occurred in the abundances of microbial carbohydrate utilization genes in response to polydextrose, but not in response to fructooligosaccharides. Using MC-TIMME2, we produced detailed, high-resolution temporal maps of the microbiota in response to glycans within and across microbiomes.

Conclusions

Our findings indicate that dietary glycans cause reproducible, dynamic, and differential alterations to the community structure of the human microbiome.
Knockout of butyrophilin subfamily 1 member A1 (BTN1A1) alters lipid droplet formation and phospholipid composition in bovine mammary epithelial cells
Authors: Han Liqiang , Zhang Menglu , Xing Zhiyang , Coleman Danielle N. , Liang Yusheng , Loor Juan J. , Yang Guoyu
Published: July 2020

Background

Milk lipids originate from cytoplasmic lipid droplets (LD) that are synthesized and secreted from mammary epithelial cells by a unique membrane-envelopment process. Butyrophilin 1A1 (BTN1A1) is one of the membrane proteins that surrounds LD, but its role in bovine mammary lipid droplet synthesis and secretion is not well known.

Methods

The objective was to knockout BTN1A1 in bovine mammary epithelial cells (BMEC) via the CRISPR/Cas9 system and evaluate LD formation, abundance of lipogenic enzymes, and content of cell membrane phospholipid (PL) species. Average LD diameter was determined via Oil Red O staining, and profiling of cell membrane phospholipid species via liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results

Lentivirus-mediated infection of the Cas9/sgRNA expression vector into BMEC resulted in production of a homozygous clone BTN1A1(−/−). The LD size and content decreased following BTN1A1 gene knockout. The mRNA abundance of fatty acid synthase (FASN) and peroxisome proliferator-activated receptor-gamma (PPARG) was downregulated in the BTN1A1(−/−) clone. Subcellular analyses indicated that BTN1A1 and LD were co-localized in the cytoplasm. BTN1A1 gene knockout increased the percentage of phosphatidylethanolamine (PE) and decreased phosphatidylcholine (PC), which resulted in a lower PC/PE ratio.

Conclusions

Results suggest that BTN1A1 plays an important role in regulating LD synthesis via a mechanism involving membrane phospholipid composition.
Efficacy and safety of tranexamic acid administration in traumatic brain injury patients: a systematic review and meta-analysis
Authors: Yokobori Shoji , Yatabe Tomoaki , Kondo Yutaka , Kinoshita Kosaku ,   for the Japan Resuscitation Council (JRC) Neuroresuscitation Task Force and the Guidelines Editorial Committee, Ajimi Yasuhiko , Iwase Masaaki , Unemoto Kyoko , Kumasawa Junji , Goto Jun , Kobata Hitoshi , Sawamura Atsushi , Hifumi Toru , Hoshiyama Eisei , Honda Mitsuru , Norisue Yasuhiro , Matsumoto Shoji , Miyake Yasufumi , Moriya Takashi , Yasuda Hideto , Yamakawa Kazuma , Yang Sunghoon , Wakasugi Masahiro , Nagayama Masao , Nonogi Hiroshi
Published: July 2020

Background

The exacerbation of intracranial bleeding is critical in traumatic brain injury (TBI) patients. Tranexamic acid (TXA) has been used to improve outcomes in TBI patient. However, the effectiveness of TXA treatment remains unclear. This study aimed to assess the effect of administration of TXA on clinical outcomes in patients with TBI by systematically reviewing the literature and synthesizing evidence of randomized controlled trials (RCTs).

Methods

MEDLINE, the Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (ICHUSHI) Web were searched. Selection criteria included randomized controlled trials with clinical outcomes of adult TBI patients administered TXA or placebo within 24 h after admission. Two investigators independently screened citations and conducted data extraction. The primary “critical” outcome was all-cause mortality. The secondary “important” outcomes were good neurological outcome rates, enlargement of bleeding, incidence of ischemia, and hemorrhagic intracranial complications. Random effect estimators with weights calculated by the inverse variance method were used to report risk ratios (RRs).

Results

A total of 640 records were screened. Seven studies were included for quantitative analysis. Of 10,044 patients from seven of the included studies, 5076 were randomly assigned to the TXA treatment group, and 4968 were assigned to placebo. In the TXA treatment group, 914 patients (18.0%) died, while 961 patients (19.3%) died in the placebo group. There was no significant difference between groups (RR, 0.93; 95% confidence interval, 0.86–1.01). No significant differences between the groups in other important outcomes were also observed.

Conclusions

TXA treatment demonstrated a tendency to reduce head trauma-related deaths in the TBI population, with no significant incidence of thromboembolic events. TXA treatment may therefore be suggested in the initial TBI care.
Role of preemptive chlorpheniramine maleate in reducing postoperative agitation after functional endoscopic sinus surgeries (FESS)
Authors: Abdelrahman Tamer Nabil , Kasem Amr Ahmed
Published: July 2020

Background

Agitation with general anesthesia for ear, nose, and throat (ENT) surgeries was so frequent reaching up to 55.4%. Chlorpheniramine maleate a first-generation antihistaminic that antagonizes histamine H1-receptor. It is specifically a potent inverse agonist of the histamine H1 receptor. It is mainly used as an anti-allergic but has some anti-depressant and anti-anxiety actions, with unknown mechanism as well.

The aim is to identify the role of preemptive chlorpheniramine maleate on alleviating or reducing the severity of postoperative agitation following FESS procedures.

Subjects and methods

A total of 90 adult patients undergoing FESS procedure for chronic sinusitis with bilateral postoperative nasal packing. Patients were randomly assigned into two equal groups. The first group (A) 45 patients received chlorpheniramine maleate 5 mg diluted in 9 ml isotonic saline IV 30 min preinduction of general anesthesia while the second group (B) received 10 ml isotonic saline IV as control.

Statistical analysis

It was done using the Statistical Package for Social Sciences (SPSS/version 21) software using arithmetic mean, standard deviation, chi square test, Fisher exact test and t test. The level of significance was 0.05.

Results

The degree of agitation measured by (RASS) and the number of patients needed midazolam and its total dose given to reduce severity of agitation postoperatively was remarkably less in group (A) than group (B).

Conclusion

Preoperative single dose of chlorpheniramine maleate is an effective medication that may be used to prevent or reduce the severity of emergence agitation with minimal cardio-respiratory depression.
Evaluation of the fungal activity of Beauveria bassiana, Metarhizium anisopliae and Paecilomyces lilacinus as biocontrol agents against root-knot nematode, Meloidogyne incognita on cowpea
Authors: Youssef Mahmoud M. A. , El-Nagdi Wafaa M. A. , Lotfy Dalia E. M.
Published: July 2020

Background

In the current years, nematotoxic or antagonistic compounds for example, toxins, enzymes, or compounds derived from the metabolites of fungal culture filtrates have greatly increased.

Objective

This research was designed to evaluate two fungi, Beauveria bassiana and Metarhizium anisopliae, commonly used only as bio-insecticides in Egypt for their nematicidal potential compared to Paecilomyces lilacinus, one of the most important fungi parasitizing on eggs of root-knot nematode, Meloidogyne incognita.

Results

The tested fungi either as filtrate or spore affected egg hatching and survival of second stage juveniles at different degrees according to fungal filtrate dilution and spore concentration and exposure period under in vitro study. Under screen house conditions, the tested fungi as filtrates or spores were used to control root-knot nematode on cowpea. The overtopped significant results were gained with P. lilacinus filtrate at standard dilution and recorded the highest mean overall percentages nematode reduction (84.5%). The second rank was obtained by B. bassiana culture filtrate, where it significantly reduced all nematode numbers with a mean of 81.1% at standard dilution. M. anisopliae caused 78.5% as a mean percentages nematode reduction followed by other dilutions and untreated check. When using spore concentrations, the overtopped significant results were gained with P. lilacinus at the highest spore concentration (1 × 108) and recorded the highest mean percentages nematode reduction (85.3%). The second rank was obtained by M. anisopliae, where it reduced all nematode numbers as an average of 83.6%. B. bassiana caused 77.1% as a mean percentages nematode reduction at the highest spore concentration. At all cases, all treatments significantly promoted plant growth and yield criteria and these increases were positively proportional to the filtrate dilution or spore concentration higher than the untreated plants.

Conclusions

It can be concluded that B. bassiana, M. Anisopliae, and P. lilacinus as antagonistic fungi proved to be efficient against root-knot nematode, incognita infecting cowpea as they reduced nematode criteria which subsequently improved plant growth and yield of cowpea.
Geophysics Bright Spots
Authors: Behura Jyoti
Published: July 2020

Welcome to the latest installment of Geophysics Bright Spots. For most of us, the pandemic has upended our daily routines. Personally, a minor silver lining in all of this chaos has been the gain of a few extra hours every week. I have used this time to catch up on the fascinating work being done in the field of artificial intelligence and its applications to numerous disciplines. An emerging trend is physics-informed machine learning, which will help us bridge the gap between traditional theoretical approaches and more recent data-driven methodologies, leading to physically plausible and meaningful results. To follow is a list of research that the editors found interesting in the latest issue of Geophysics. I sincerely hope these articles enlighten you and take your mind off some of the chaos surrounding us.
Stress, Sex, and Sugar: Glucocorticoids and Sex-Steroid Crosstalk in the Sex-Specific Misprogramming of Metabolism
Authors: Ruiz Daniel , Padmanabhan Vasantha , Sargis Robert M
Published: July 2020

Early-life exposures to environmental insults can misprogram development and increase metabolic disease risk in a sex-dependent manner by mechanisms that remain poorly characterized. Modifiable factors of increasing public health relevance, such as diet, psychological stress, and endocrine-disrupting chemicals, can affect glucocorticoid receptor signaling during gestation and lead to sex-specific postnatal metabolic derangements. Evidence from humans and animal studies indicate that glucocorticoids crosstalk with sex steroids by several mechanisms in multiple tissues and can affect sex-steroid–dependent developmental processes. Nonetheless, glucocorticoid sex-steroid crosstalk has not been considered in the glucocorticoid-induced misprogramming of metabolism. Herein we review what is known about the mechanisms by which glucocorticoids crosstalk with estrogen, androgen, and progestogen action. We propose that glucocorticoid sex-steroid crosstalk is an understudied mechanism of action that requires consideration when examining the developmental misprogramming of metabolism, especially when assessing sex-specific outcomes.
Effects of Testosterone on Serum Concentrations, Fat-free Mass, and Physical Performance by Population: A Meta-analysis
Authors: Varanoske Alyssa N , Margolis Lee M , Pasiakos Stefan M
Published: July 2020

Testosterone (T) administration (TA) increases serum T and fat-free mass (FFM). Although TA-mediated increases in FFM may enhance physical performance, the data are largely equivocal, which may be due to differences in study populations, the magnitude of change in serum T and FFM, or the performance metrics. This meta-analysis explored effects of TA on serum T, FFM, and performance. Associations between increases in serum T and FFM were assessed, and whether changes in serum T or FFM, study population, or the performance metrics affected performance was determined. A systematic review of double-blind randomized trials comparing TA versus placebo on serum T, FFM, and performance was performed. Data were extracted from 20 manuscripts. Effect sizes (ESs) were assessed using Hedge’s g and a random effects model. Data are presented as ES (95% confidence interval). No significant correlation between changes in serum T and FFM was observed (P = .167). Greater increases in serum T, but not FFM, resulted in larger effects on performance. Larger increases in testosterone (7.26 [0.76-13.75]) and FFM (0.80 [0.20-1.41]) were observed in young males, but performance only improved in diseased (0.16 [0.05-0.28]) and older males (0.19 [0.10-0.29]). TA increased lower body (0.12 [0.07-0.18]), upper body (0.26 [0.11-0.40]), and handgrip (0.13 [0.04-0.22]) strength, lower body muscular endurance (0.38 [0.09-0.68]), and functional performance (0.20 [0.00-0.41]), but not lower body power or aerobic endurance. TA elicits increases in serum T and FFM in younger, older, and diseased males; however, the performance-enhancing effects of TA across studies were small, observed mostly in muscular strength and endurance, and only in older and diseased males.
Mechanisms of heart valve development and disease
Authors: O'Donnell Anna , Yutzey Katherine E.
Published: July 2020

The valves of the heart are crucial for ensuring that blood flows in one direction from the heart, through the lungs and back to the rest of the body. Heart valve development is regulated by complex interactions between different cardiac cell types and is subject to blood flow-driven forces. Recent work has begun to elucidate the important roles of developmental pathways, valve cell heterogeneity and hemodynamics in determining the structure and function of developing valves. Furthermore, this work has revealed that many key genetic pathways involved in cardiac valve development are also implicated in diseased valves. Here, we review recent discoveries that have furthered our understanding of the molecular, cellular and mechanosensitive mechanisms of valve development, and highlight new insights into congenital and acquired valve disease.
Oocytes and hypoxanthine orchestrate the G2-M switch mechanism in ovarian granulosa cells
Authors: Li Chengyu , Meng Xueqin , Liu Shuo , Li Weijian , Zhang Xue , Zhou Jilong , Yao Wang , Dong Chao , Liu Zhaojun , Zhou Jiaqi , Li Juan , Tao Jingli , Wu Wangjun , Shen Ming , Liu Honglin
Published: July 2020

In mammalian growing follicles, oocytes are arrested at the diplotene stage (which resembles the G2/M boundary in mitosis), while the granulosa cells (GCs) continue to proliferate during follicular development, reflecting a cell cycle asynchrony between oocytes and GCs. Hypoxanthine (Hx), a purine present in the follicular fluid, has been shown to induce oocytes meiotic arrest, although its role in GC proliferation remains ill-defined. Here, we demonstrate that Hx indiscriminately prevents G2-to-M phase transition in porcine GCs. However, oocyte-derived paracrine factors (ODPFs), particularly GDF9 and BMP15, maintain the proliferation of GCs, partly by activating the ERK1/2 signaling and enabling the G2/M transition that is suppressed by Hx. Interestingly, GCs with lower expression of GDF9/BMP15 receptors appear to be more sensitive to Hx-induced G2/M arrest and become easily detached from the follicular wall. Importantly, Hx-mediated inhibition of G2/M progression instigates GC apoptosis, which is ameliorated in the presence of GDF9 and/or BMP15. Therefore, our data indicate that the counterbalance of intrafollicular factors, particularly Hx and oocyte-derived GDF9/BMP15, fine-tunes the development of porcine follicles by regulating the cell cycle progression of GCs.
Circulating exosomal microRNAs as potential biomarkers of hepatic injury and inflammation in a murine model of glycogen storage disease type 1a
Authors: Resaz Roberta , Cangelosi Davide , Morini Martina , Segalerba Daniela , Mastracci Luca , Grillo Federica , Bosco Maria Carla , Bottino Cristina , Colombo Irma , Eva Alessandra
Published: July 2020

Most patients affected by glycogen storage disease type 1a (GSD1a), an inherited metabolic disorder caused by mutations in the enzyme glucose-6-phosphatase-α (G6Pase-α), develop renal and liver complications, including the development of hepatocellular adenoma/carcinoma. The purpose of this study was to identify potential biomarkers of the pathophysiology of the GSD1a-affected liver. To this end, we used the plasma exosomes of a murine model of GSD1a, the LS-G6pc−/− mouse, to uncover the modulation in microRNA expression associated with the disease. The microRNAs differentially expressed between LS-G6pc−/− and wild-type mice, LS-G6pc−/− mice with hepatocellular adenoma and LS-G6pc−/− mice without adenoma, and LS-G6pc−/− mice with amyloidosis and LS-G6pc−/− mice without amyloidosis were identified. Pathway analysis demonstrated that the target genes of the differentially expressed microRNA were significantly enriched for the insulin signaling pathway, glucose and lipid metabolism, Wnt/β-catenin, telomere maintenance and hepatocellular carcinoma, and chemokine and immune regulation signaling pathways. Although some microRNAs were common to the different pathologic conditions, others were unique to the cancerous or inflammatory status of the animals. Therefore, the altered expression of several microRNAs is correlated with various pathologic liver states and might help to distinguish them during the progression of the disease and the development of late GSD1a-associated complications.
miR-206 enforces a slow muscle phenotype
Authors: Bjorkman Kristen K. , Guess Martin G. , Harrison Brooke C. , Polmear Michael M. , Peter Angela K. , Leinwand Leslie A.
Published: July 2020

Striated muscle is a highly specialized collection of tissues with contractile properties that vary according to functional needs. Although muscle fiber types are established postnatally, lifelong plasticity facilitates stimulus-dependent adaptation. Functional adaptation requires molecular adaptation, which is partially provided by miRNA-mediated post-transcriptional regulation. miR-206 is a muscle-specific miRNA enriched in slow muscles. We investigated whether miR-206 drives the slow muscle phenotype or is merely an outcome. We found that miR-206 expression increases in both physiological (including female sex and endurance exercise) and pathological conditions (muscular dystrophy and adrenergic agonism) that promote a slow phenotype. Consistent with that observation, the slow soleus muscle of male miR-206-knockout mice displays a faster phenotype than wild-type mice. Moreover, left ventricles of male miR-206 knockout mice have a faster myosin profile, accompanied by dilation and systolic dysfunction. Thus, miR-206 appears to be necessary to enforce a slow skeletal and cardiac muscle phenotype and to play a key role in muscle sexual dimorphisms.
Nest predation and adult mortality relationships with post-natal metabolic rates and growth among songbird species
Authors: Ton Riccardo , Martin Thomas E.
Published: July 2020

Metabolism is thought to mediate the connection between environmental selection pressures and a broad array of life history tradeoffs, but tests are needed. High juvenile predation correlates with fast growth, which may be achieved via fast juvenile metabolism. Fast offspring metabolism and growth can create physiological costs later in life that should be minimized in species with low adult mortality. Yet, relations between juvenile metabolism and mortality at offspring versus adult stages are unexplored. We found that post-natal metabolism was positively correlated with adult mortality but not nest predation rates among 43 songbird species on three continents. Nest predation, but not adult mortality, explained additional variation in growth rates beyond metabolism. Our results suggest that metabolism may not be the mechanism underlying the relations between growth and mortality at different life stages.
The association of socio-demographic and environmental factors on childhood diarrhea in Cambodia
Authors: Pisey Vong , Banchonhattakit Pannee
Published: July 2020

Background: Diarrhea is still the leading cause of childhood death worldwide, as well as a major cause for concern in developing countries. This study was conducted to investigate the factors related to childhood diarrhea in Cambodia.

Methods: A cross-sectional study of the secondary data from the Cambodia Demographic and Health Survey 2014 was conducted using the combination of household data and children’s data. A generalized linear mixed model was used to analyze the determinant factors of childhood diarrhea.

Results: The surveys included 2,828 children, aged 12 to 35 months. The prevalence of diarrhea in the last 2 weeks was 16.44% (95% CI: 14.72%-18.31%). Factors with statistically significant associations with childhood diarrhea in Cambodia were: maternal  unemployment, compared with being in employment (AOR = 1.43; 95% CI: 1.14-1.78); the child being male (AOR = 1.25; 95%CI: 1.02-1.53); the presence of unimproved toilet facilities (AOR = 1.17; 95%CI: 1.05-1.31) compared with improved toilet facilities; and unhygienic disposal of children’s stools (AOR = 1.32; 95%CI: 1.06-1.64) compared with hygienic disposal of children’s stools when controlling for other covariates. Both maternal age (one year older; AOR = 0.85; 95%CI: 0.78– 0.93) and child age (one month older; AOR = 0.86; 95%CI: 0.78-0.94) had significant negative associations with the occurrence of childhood diarrhea.

Conclusion: Childhood diarrhea remains a public health concern in Cambodia. The probability of diarrhea occurring is shown to be increased by maternal unemployment, the sex of the child being male, lack of provision of improved toilet facilities, and the unhygienic disposal of children’s stools; whereas increasing maternal age and child’s age were associated with a reduced chance of diarrhea occurring. On the basis of these results, we recommend provision of programs focusing on reducing diarrhea through the construction of improved toilet facilities and the promotion of behavior to improve hygiene, specifically targeting younger mothers.