bluuebunny/crossref_metadata_2025 huggingface dataset:
Does medication administration affect the rate of orthodontic tooth movement and root resorption development in humans? A systematic review
Authors: Kaklamanos Eleftherios G , Makrygiannakis Miltiadis A , Athanasiou Athanasios E
Published: July 2019

Background

Recently, the potential impact of different medications on the rate of orthodontic tooth movement and the associated root resorption has been systematically reviewed in animal studies and various effects have been shown. However, animal data cannot be extrapolated to human clinical situations directly.

Objectives

To systematically investigate the most up to date available evidence from controlled human studies regarding the effect of medication administration on the rate of orthodontic tooth movement and associated root resorption development.

Search methods

We searched eight databases (covering also grey literature) without restrictions and we performed hand searching up until October 2018.

Selection criteria

Controlled studies in humans assessing the effect of various medications on the rate of orthodontic tooth movement and root resorption development.

Data collection and analysis

Study selection was followed by data extraction and risk of bias assessment using the ROBINS-I tool for non-randomized and the Cochrane Risk of Bias Tool for randomized studies.

Results

Eight studies, at various risk of bias, were finally identified. With regard to the rate of orthodontic tooth movement, local injections of prostaglandin E1 were found to exert an increasing effect, whereas systemic intake of nabumetone decreased it. Following tenoxicam administration, drinking water with fluoride or local injections of calcitriol (vitamin D metabolite), no significant effects were demonstrated. Concerning root resorption development, nabumetone administration was shown to reduce it, whereas fluoride, overall, was not observed to exert any effect. Only in individuals subjected to heavy orthodontic forces, did fluoride show a protective effect for the period of force application, but not in the longer term during retention.

Conclusions

The aforementioned substances may show varying effects on the rate of orthodontic tooth movement and root resorption development in human subjects. Despite the observed limitations, the orthodontist should be able to identify patients taking pharmaceuticals and consider any implications related to orthodontic treatment.

Registration

PROSPERO (CRD42017078208).
One Order Fits All? Birth Order and Education in Immigrant Families
Authors: Isungset Martin Arstad , Lillehagen Mats , Ugreninov Elisabeth
Published: July 2019

Birth order causes social inequality between siblings. In Western countries, earlier-born perform better than later-born. In non-Western countries, however, earlier-born generally perform worse than later-born. We use administrative data to compare birth order effects between the native population and Norwegian-born children of immigrants (450,864 individuals nested within 202,191 families). The outcome is based on lower secondary school points—a combined measurement of all marks at the end of compulsory education. We found negative effects of birth order on school points for Norwegian natives. This finding is in line with previous studies from Western countries using measures of educational achievement. Birth order effects amongst Norwegian-born children of immigrant parents vary according to maternal country of origin, with some displaying similar effects as natives and others displaying no birth order effects. These findings are surprising in light of the main theories on birth order, which are universalistic and do not predict group-differences. We argue that the universalistic theories need to be supplemented to account for our findings, and discuss the potential importance of cultural variation in family-related behaviours such as strategic parenting, kindergarten attendance, and peer-influence in high-achieving immigrant groups.
Short-term diuretic withdrawal in stable outpatients with mild heart failure and no fluid retention receiving optimal therapy: a double-blind, multicentre, randomized trial
Authors: Rohde Luis E , Rover Marciane M , Figueiredo Neto Jose A , Danzmann Luiz C , Bertoldi Eduardo G , Simões Marcus V , Silvestre Odilson M , Ribeiro Antonio L P , Moura Lidia Zytynski , Beck-da-Silva Luis , Prado Debora , Sant'Anna Roberto T , Bridi Leonardo H , Zimerman André , Raupp da Rosa Priscila , Biolo Andréia
Published: July 2019

Aims

Although loop diuretics are widely used to treat heart failure (HF), there is scarce contemporary data to guide diuretic adjustments in the outpatient setting.

Methods and results

In a prospective, randomized and double-blind protocol, we tested the safety and tolerability of withdrawing low-dose furosemide in stable HF outpatients at 11 HF clinics in Brazil. The trial had two blindly adjudicated co-primary outcomes: (i) symptoms assessment quantified as the area under the curve (AUC) of a dyspnoea score on a visual-analogue scale evaluated at 4 time-points (baseline, Day 15, Day 45, and Day 90) and (ii) the proportion of patients maintained without diuretic reuse during follow-up. We enrolled 188 patients (25% females; 59 ± 13 years old; left ventricular ejection fraction = 32 ± 8%) that were randomized to furosemide withdrawal (n = 95) or maintenance (n = 93). For the first co-primary endpoint, no significant difference in patients’ assessment of dyspnoea was observed in the comparison of furosemide withdrawal with continuous administration [median AUC 1875 (interquartile range, IQR 383–3360) and 1541 (IQR 474–3124), respectively; P = 0.94]. For the second co-primary endpoint, 70 patients (75.3%) in the withdrawal group and 77 patients (83.7%) in the maintenance group were free of furosemide reuse during follow-up (odds ratio for additional furosemide use with withdrawal 1.69, 95% confidence interval 0.82–3.49; P = 0.16). Heart failure-related events (hospitalizations, emergency room visits, and deaths) were infrequent and similar between groups (P = 1.0).

Conclusions

Diuretic withdrawal did not result in neither increased self-perception of dyspnoea nor increased need of furosemide reuse. Diuretic discontinuation may deserve consideration in stable outpatients with no signs of fluid retention receiving optimal medical therapy.

ClinicalTrials.gov Identifier

NCT02689180.
Type 8 long QT syndrome: pathogenic variants in CACNA1C-encoded Cav1.2 cluster in STAC protein binding site
Authors: Mellor Greg J , Panwar Pankaj , Lee Andrea K , Steinberg Christian , Hathaway Julie A , Bartels Kirsten , Christian Susan , Balaji Seshadri , Roberts Jason D , Simpson Chris S , Boczek Nicole J , Tester David J , Radbill Andrew E , Mok Ngai-Shing , Hamilton Robert M , Kaufman Elizabeth S , Eugenio Paul L , Weiss Raul , January Craig , McDaniel George M , Leather Richard A , Erickson Christopher , Falik Shelley , Behr Elijah R , Wilde Arthur A M , Sanatani Shubhayan , Ackerman Michael J , Van Petegem Filip , Krahn Andrew D , Laksman Zachary
Published: July 2019

Aims

Pathogenic gain-of-function variants in CACAN1C cause type-8 long QT syndrome (LQT8). We sought to describe the electrocardiographic features in LQT8 and utilize molecular modelling to gain mechanistic insights into its genetic culprits.

Methods and results

Rare variants in CACNA1C were identified from genetic testing laboratories. Treating physicians provided clinical information. Variant pathogenicity was independently assessed according to recent guidelines. Pathogenic (P) and likely pathogenic (LP) variants were mapped onto a 3D modelled structure of the Cav1.2 protein. Nine P/LP variants, identified in 23 patients from 19 families with non-syndromic LQTS were identified. Six variants, found in 79% of families, clustered to a 4-residue section in the cytosolic II–III loop region which forms a region capable of binding STAC SH3 domains. Therefore, variants may affect binding of SH3-domain containing proteins. Arrhythmic events occurred in similar proportions of patients with II–III loop variants and with other P/LP variants (53% vs. 48%, P = 0.41) despite shorter QTc intervals (477 ± 31 ms vs. 515 ± 37 ms, P = 0.03). A history of sudden death was reported only in families with II–III loop variants (60% vs. 0%, P = 0.03). The predominant T-wave morphology was a late peaking T wave with a steep descending limb. Exercise testing demonstrated QTc prolongation on standing and at 4 min recovery after exercise.

Conclusion

The majority of P/LP variants in patients with CACNA1C-mediated LQT8 cluster in an SH3-binding domain of the cytosolic II–III loop. This represents a ‘mutation hotspot’ in LQT8. A late-peaking T wave with a steep descending limb and QT prolongation on exercise are commonly seen.
Understanding rapid infant weight gain prevention: a systematic review of quantitative and qualitative evidence
Authors: Rotevatn Torill A , Melendez-Torres G J , Overgaard Charlotte , Peven Kimberly , Hyldgaard Nilsen Jane , Bøggild Henrik , Høstgaard Anna Marie Balling
Published: July 2019

Background

Rapid infant weight gain (RIWG) is strongly related to childhood overweight and obesity, and prevention of RIWG is an approach to early years obesity prevention. This systematic review aimed to explore effectiveness, deliverers’ and recipients’ experiences of involvement, and key intervention components and processes of such prevention activities.

Methods

Key databases and websites were searched systematically for quantitative and qualitative studies covering intervention effectiveness, experiences with intervention involvement or process outcomes. After duplicate screening and quality assessment, papers were analyzed through narrative synthesis, thematic synthesis and intervention component analysis.

Results

Seven quantitative and seven qualitative studies were eligible for inclusion. Most intervention studies reported small, but significant results on infant weight gain. More significant results were measured on weight gain during the first compared with the second year of life. A weak evidence base made elaboration of the relationship between intervention effectiveness and content challenging. Home-delivered interventions may be more relevant for parents. Contextual factors, such as social norms, beliefs and professional identity should be considered during intervention development. Stakeholder involvement can be key to increase intervention acceptability and feasibility.

Conclusions

The field of RIWG prevention is new and evolving, but more research is needed before further conclusions about intervention effectiveness and intervention content can be drawn. Future interventions should take parents, health professionals and other contextual needs into account to improve chances of success. More research on long-term effects on overweight and obesity is needed.
Doses of hepatitis B revaccination needed for the seronegative youths to be seropositive to antibody against hepatitis B surface antigen
Authors: Jan Chyi-Feng , Liu Tzu-Hung , Ho Chien-Han , Chien Yin-Chu , Chang Che-Jui , Guo Fei-Ran , Huang Kuo-Chin
Published: July 2019

Objectives

To determine the required hepatitis B vaccine doses for subjects who were seronegative for three hepatitis B seromarkers during their youth who wish to have seroprotective antibodies against the hepatitis B surface antigen (anti-HBs).

Methods

We conducted a retrospective cohort study. From 2012 to 2015, graduate school students born after 1986 who were seronegative for three hepatitis B virus seromarkers at college entrance (n = 1037) were recruited. Four groups of subjects received zero to three doses of a hepatitis B vaccine booster at their free willingness, and their anti-HBs titre were measured at their graduate school entrance. Very low and extremely low antibody titres against the hepatitis B surface antigen were elucidated by graphic inference to determine the required booster dose cut-off value for seropositivity after revaccination.

Results

The anti-HBs seropositive rates in the four groups of subjects receiving the hepatitis B booster vaccine(s) were 17.7%, 52.1%, 78.6% and 90.9% for those receiving zero, one, two and three doses, respectively. In subjects with very low antibody titres against the hepatitis B surface antigen after one dose of the vaccine booster and subjects with an extremely low titre after two doses of the booster, the seropositive rates reached 95% at the cut-off value of 3 mIU/ml.

Conclusion

A seropositive rate of at least 95% can be reached by the administration of two hepatitis B booster doses to youths with extremely low antibody titres against the hepatitis B surface antigen (<3 mIU/ml) and administering one dose to those with very low titres (3–10 mIU/ml) at college.
Use of perioperative chemotherapy in colorectal cancer metastatic to the liver
Authors: Symonds Lynn K , Cohen Stacey A
Published: July 2019

A curative-intent approach may improve survival in carefully selected patients with oligometastatic colorectal cancer. Aggressive treatments are most frequently administered to patients with isolated liver metastasis, though they may be judiciously considered for other sites of metastasis. To be considered for curative intent with surgery, patients must have disease that can be definitively treated while leaving a sufficient functional liver remnant. Neoadjuvant chemotherapy may be used for upfront resectable disease as a test of tumor biology and/or for upfront unresectable disease to increase the likelihood of resectability (so-called ‘conversion’ chemotherapy). While conversion chemotherapy in this setting aims to improve survival, the choice of a regimen remains a complex and highly individualized decision. In this review, we discuss the role of RAS status, primary site, sidedness, and other clinical features that affect chemotherapy treatment selection as well as key factors of patients that guide individualized patient-treatment recommendations for colorectal-cancer patients being considered for definitive treatment with metastasectomy.
Shared Pathogenomic Patterns Characterize a New Phylotype, Revealing Transition toward Host-Adaptation Long before Speciation of Mycobacterium tuberculosis
Authors: Sapriel Guillaume , Brosch Roland
Published: July 2019

Tuberculosis remains one of the deadliest infectious diseases of humanity. To better understand the evolutionary history of host-adaptation of tubercle bacilli (MTB), we sought for mycobacterial species that were more closely related to MTB than the previously used comparator species Mycobacterium marinum and Mycobacterium kansasii. Our phylogenomic approach revealed some recently sequenced opportunistic mycobacterial pathogens, Mycobacterium decipiens, Mycobacterium lacus, Mycobacterium riyadhense, and Mycobacterium shinjukuense, to constitute a common clade with MTB, hereafter called MTB-associated phylotype (MTBAP), from which MTB have emerged. Multivariate and clustering analyses of genomic functional content revealed that the MTBAP lineage forms a clearly distinct cluster of species that share common genomic characteristics, such as loss of core genes, shift in dN/dS ratios, and massive expansion of toxin–antitoxin systems. Consistently, analysis of predicted horizontal gene transfer regions suggests that putative functions acquired by MTBAP members were markedly associated with changes in microbial ecology, for example adaption to intracellular stress resistance. Our study thus considerably deepens our view on MTB evolutionary history, unveiling a decisive shift that promoted conversion to host-adaptation among ancestral founders of the MTBAP lineage long before Mycobacterium tuberculosis has adapted to the human host.
Multilocus Analysis Resolves the European Finch Epidemic Strain of Trichomonas gallinae and Suggests Introgression from Divergent Trichomonads
Authors: Alrefaei Abdulwahed Fahad , Low Ross , Hall Neil , Jardim Rodrigo , Dávila Alberto , Gerhold Rick , John Shinto , Steinbiss Sascha , Cunningham Andrew A , Lawson Becki , Bell Diana , Tyler Kevin
Published: July 2019

In Europe, Trichomonas gallinae recently emerged as a cause of epidemic disease in songbirds. A clonal strain of the parasite, first found in the United Kingdom, has become the predominant strain there and spread to continental Europe. Discriminating this epidemic strain of T. gallinae from other strains necessitated development of multilocus sequence typing (MLST). Development of the MLST was facilitated by the assembly and annotation of a 54.7 Mb draft genome of a cloned stabilate of the A1 European finch epidemic strain (isolated from Greenfinch, Chloris chloris, XT-1081/07 in 2007) containing 21,924 protein coding genes. This enabled construction of a robust 19 locus MLST based on existing typing loci for Trichomonas vaginalis and T. gallinae. Our MLST has the sensitivity to discriminate strains within existing genotypes confidently, and resolves the American finch A1 genotype from the European finch epidemic A1 genotype. Interestingly, one isolate we obtained from a captive black-naped fruit dove Ptilinopsus melanospilus, was not truly T. gallinae but a hybrid of T. gallinae with a distant trichomonad lineage. Phylogenetic analysis of the individual loci in this fruit dove provides evidence of gene flow between distant trichomonad lineages at 2 of the 19 loci examined and may provide precedence for the emergence of other hybrid trichomonad genomes including T. vaginalis.
Intraspecific Diversity of Fission Yeast Mitochondrial Genomes
Authors: Tao Yu-Tian , Suo Fang , Tusso Sergio , Wang Yan-Kai , Huang Song , Wolf Jochen B W , Du Li-Lin
Published: July 2019

The fission yeast Schizosaccharomyces pombe is an important model organism, but its natural diversity and evolutionary history remain under-studied. In particular, the population genomics of the S. pombe mitochondrial genome (mitogenome) has not been thoroughly investigated. Here, we assembled the complete circular-mapping mitogenomes of 192 S. pombe isolates de novo, and found that these mitogenomes belong to 69 nonidentical sequence types ranging from 17,618 to 26,910 bp in length. Using the assembled mitogenomes, we identified 20 errors in the reference mitogenome and discovered two previously unknown mitochondrial introns. Analyzing sequence diversity of these 69 types of mitogenomes revealed two highly distinct clades, with only three mitogenomes exhibiting signs of inter-clade recombination. This diversity pattern suggests that currently available S. pombe isolates descend from two long-separated ancestral lineages. This conclusion is corroborated by the diversity pattern of the recombination-repressed K-region located between donor mating-type loci mat2 and mat3 in the nuclear genome. We estimated that the two ancestral S. pombe lineages diverged about 31 million generations ago. These findings shed new light on the evolution of S. pombe and the data sets generated in this study will facilitate future research on genome evolution.
Slip distribution of the 2017 Mw6.6 Bodrum–Kos earthquake: resolving the ambiguity of fault geometry
Authors: Konca A Ozgun , Guvercin Sezim Ezgi , Ozarpaci Seda , Ozdemir Alpay , Funning Gareth J , Dogan Ugur , Ergintav Semih , Floyd Michael , Karabulut Hayrullah , Reilinger Robert
Published: July 2019

The 2017 July 20, Mw6.6 Bodrum–Kos earthquake occurred in the Gulf of Gökova in the SE Aegean, a region characterized by N–S extension in the backarc of the easternmost Hellenic Trench. The dip direction of the fault that ruptured during the earthquake has been a matter of controversy where both north- and south-dipping fault planes were used to model the coseismic slip in previous studies. Here, we use seismic (seismicity, main shock modelling, aftershock relocations and aftershock mechanisms using regional body and surface waves), geodetic (GPS, InSAR) and structural observations to estimate the location, and the dip direction of the fault that ruptured during the 2017 earthquake, and the relationship of this event to regional tectonics. We consider both dip directions and systematically search for the best-fitting locations for the north- and south-dipping fault planes. Comparing the best-fitting planes for both dip directions in terms of their misfit to the geodetic data, proximity to the hypocenter location and Coulomb stress changes at the aftershock locations, we conclude that the 2017 earthquake ruptured a north-dipping fault. We find that the earthquake occurred on a 20–25 km long, ∼E–W striking, 40° north-dipping, pure normal fault with slip primarily confined between 3 and 15 km depth, and the largest slip exceeding 2 m between depths of 4 and 10 km. The coseismic fault, not mapped previously, projects to the surface within the western Gulf, and partly serves both to widen the Gulf and separate Kos Island from the Bodrum Peninsula of SW Anatolia. The coseismic fault may be an extension of a mapped, north-dipping normal fault along the south side of the Gulf of Gökova. While all of the larger aftershocks are consistent with N–S extension, their spatially dispersed pattern attests to the high degree of crustal fracturing within the basin, due to rapid trenchward extension and anticlockwise rotation within the southeastern Aegean.
Updated attenuation tomography of Japan subduction zone
Authors: Wang Zewei , Zhao Dapeng
Published: July 2019

We determine an updated model of P- and S-wave attenuation (Qp, Qs) tomography of the Japan subduction zone using an improved inversion scheme, and derive the first Qp/Qs model of the study region. We establish a system of observation t* equations by taking 1/Q values at 3-D grid nodes arranged in the study volume as unknown parameters. This scheme can eliminate model errors caused by ignoring high-order terms of the Taylor expansion in the Q-format scheme adopted by previous studies. The inversion problem is considered as a quadratic programming problem with bound constraints for best fitting the observed t* data in a least-squares sense. The 3-D attenuation model is obtained by using a limited-memory Broyden–Fletcher–Goldfarb–Shanno algorithm for bound constrained optimization. Because this inversion scheme uses bound constraints to avoid negative Q values, damping regularization is not needed, hence the ranges of Qp and Qs values obtained are less affected by human subjectivity. The subducting Pacific and Philippine Sea slabs exhibit high-Q and high Qp/Qs, whereas the mantle wedge beneath the volcanic front and back-arc area shows low-Q and low Qp/Qs. Both Qp and Qs vary in a range of 10–2000, and the Qp/Qs ratio changes from 0.4 to 1.4. Our results reveal a narrow high-Qp/Qs belt that is coincident with the distribution of volcanic and non-volcanic low-frequency micro-earthquakes (M 0.0–2.5), which may reflect high water-saturation anomalies that are probably associated with slab-derived fluids and responsible for the generation of low-frequency micro-earthquakes.
Patient-experience during delivery in public health facilities in Uttar Pradesh, India
Authors: Montagu Dominic , Landrian Amanda , Kumar Vishwajeet , Phillips Beth S , Singhal Shreya , Mishra Shambhavi , Singh Shambhavi , Cotter Sun Yu , Singh Vinay Pratap , Kajal Fnu , Sudhinaraset May
Published: July 2019

In India, most women now delivery in hospitals or other facilities, however, maternal and neonatal mortality remains stubbornly high. Studies have shown that mistreatment causes delays in care-seeking, early discharge and poor adherence to post-delivery guidance. This study seeks to understand the variation of women’s experiences in different levels of government facilities. This information can help to guide improvement planning. We surveyed 2018 women who gave birth in a representative set of 40 government facilities from across Uttar Pradesh (UP) state in northern India. Women were asked about their experiences of care, using an established scale for person-centred care. We asked questions specific to treatment and clinical care, including whether tests such as blood pressure, contraction timing, newborn heartbeat or vaginal exams were conducted, and whether medical assessments for mothers or newborns were done prior to discharge. Women delivering in hospitals reported less attentive care than women in lower-level facilities, and were less trusting of their providers. After controlling for a range of demographic attributes, we found that better access, higher clinical quality, and lower facility-level, were all significantly predictive of patient-centred care. In UP, lower-level facilities are more accessible, women have greater trust for the providers and women report being better treated than in hospitals. For the vast majority of women who will have a safe and uncomplicated delivery, our findings suggest that the best option would be to invest in improvements mid-level facilities, with access to effective and efficient emergency referral and transportation systems should they be needed.
Attitudes, knowledge and sexual behavior among Finnish adolescents before and after an intervention
Authors: Pakarinen Marja , Kylmä Jari , Helminen Mika , Suominen Tarja
Published: July 2019

Adolescents are an important target group for sexual health promotion, and there are numerous programs and interventions carried out in this field. The aim of this study is to describe adolescents’ attitudes, knowledge and sexual behavior before and after a sexual health promotion intervention. The intervention was developed in the study and consisted of three elements: (i) class-room session, (ii) information materials and (iii) free condom distribution. The study was carried out in eight randomly selected vocational schools in Finland. The participants were first year students aged 15–19 years. The data were collected using an electronic questionnaire before intervention (intervention baseline n = 500, control baseline n = 183) and two times after the intervention (intervention first follow-up n = 173/second follow-up n = 202, control first follow-up n = 115/second follow-up n = 46). There were significant differences before and after the intervention concerning better knowledge and more frequent testing for sexually transmitted infections (STIs). Schools are an important environment to reach adolescents during the phase where their sexual health is developing and there is an increased risk of STI transmission. More school-based interventions are therefore needed, and the results of this study can be utilized when developing sexual health promotion interventions among adolescents.
Applying intersectionality theory in health promotion research and practice
Authors: Heard Emma , Fitzgerald Lisa , Wigginton Britta , Mutch Allyson
Published: July 2019

Health promotion researchers and practitioners are grappling with how to address growing health inequalities for population groups. In particular, critiques of dominant behaviour change approaches draw attention to the need to engage with social theories to better understand the social and relational drivers of health. Public health researchers are increasingly acknowledging intersectionality as an important theoretical approach, providing a framework for investigating health inequalities by highlighting intersections of individuals’ multiple identities within social systems of power that compound and exacerbate experiences of ill health. This article provides an overview of the diverse ways public health researchers and practitioners have applied intersectionality theory to better understand and address health inequalities. We map three key applications of intersectionality theory in public health: as an epistemological approach, as a methodological approach, and as a tool for action and intervention. Drawing on this work, we argue that health promotion researchers and practitioners can enhance engagement with intersectionality theory to address important challenges within the field. Through this article, we aim to inspire the continued exploration of intersectionality and offer some insights into opportunities and challenges for doing so in health promotion.
The repair of endo/exogenous DNA double-strand breaks and its effects on meiotic chromosome segregation in oocytes
Authors: Ma Jun-Yu , Feng Xie , Tian Xin-Yi , Chen Lei-Ning , Fan Xiao-Yan , Guo Lei , Li Sen , Yin Shen , Luo Shi-Ming , Ou Xiang-Hong
Published: July 2019

Germ cell-derived genomic structure variants not only drive the evolution of species but also induce developmental defects in offspring. The genomic structure variants have different types, but most of them are originated from DNA double-strand breaks (DSBs). It is still not well known whether DNA DSBs exist in adult mammalian oocytes and how the growing and fully grown oocytes repair their DNA DSBs induced by endogenous or exogenous factors. In this study, we detected the endogenous DNA DSBs in the growing and fully grown mouse oocytes and found that the DNA DSBs mainly localized at the centromere-adjacent regions, which are also copy number variation hotspots. When the exogenous DNA DSBs were introduced by Etoposide, we found that Rad51-mediated homologous recombination (HR) was used to repair the broken DNA. However, the HR repair caused the chromatin intertwined and impaired the homologous chromosome segregation in oocytes. Although we had not detected the indication about HR repair of endogenous centromere-adjacent DNA DSBs, we found that Rad52 and RNA:DNA hybrids colocalized with these DNA DSBs, indicating that a Rad52-dependent DNA repair might exist in oocytes. In summary, our results not only demonstrated an association between endogenous DNA DSBs with genomic structure variants but also revealed one specific DNA DSB repair manner in oocytes.
Tbx5 inhibits hedgehog signaling in determination of digit identity
Authors: Xu Huiting , Xiang Menglan , Qin Yushu , Cheng Henghui , Chen Duohua , Fu Qiang , Zhang Ke K , Xie Linglin
Published: July 2019

Dominant TBX5 mutation causes Holt-Oram syndrome (HOS), which is characterized by limb defects in humans, but the underlying mechanistic basis is unclear. We used a mouse model with Tbx5 conditional knockdown in Hh-receiving cells (marked by Gli1+) during E8 to E10.5, a previously established model to study atrial septum defects, which displayed polydactyly or hypodactyly. The results suggested that Tbx5 is required for digit identity in a subset of limb mesenchymal cells. Specifically, Tbx5 deletion in this cell population decreased cell apoptosis and increased the proliferation of handplate mesenchymal cells. Furthermore, Tbx5 was found to negatively regulate the Hh-signaling activity through transcriptional regulation of Ptch1, a known Hh-signaling repressor. Repression of Hh-signaling through Smo co-mutation in Tbx5 heterozygotes rescued the limb defects, thus placing Tbx5 upstream of Hh-signaling in limb defects. This work reveals an important missing component necessary for understanding not only limb development but also the molecular and genetic mechanisms underlying HOS.
Adaptation and Evolution of Biological Materials
Authors: Campbell Robert A , Dean Mason N
Published: July 2019

Research into biological materials often centers on the impressive material properties produced in Nature. In the process, however, this research often neglects the ecologies of the materials, the organismal contexts relating to how a biological material is actually used. In biology, materials are vital to organismal interactions with their environment and their physiology, and also provide records of their phylogenetic relationships and the selective pressures that drive biological novelties. With the papers in this symposium, we provide a view on cutting-edge work in biological materials science. The collected research delivers new perspectives on fundamental materials concepts, offering surprising insights into biological innovations and challenging the boundaries of materials’ characterization techniques. The topics, systems, and disciplines covered offer a glimpse into the wide range of contemporary biological materials work. They also demonstrate the need for progressive “whole organism thinking” when characterizing biological materials, and the importance of framing biological materials research in relevant, biological contexts.
Clinical usefulness of prethymectomy plasmapheresis in patients with myasthenia gravis: a systematic review and meta-analysis
Authors: Reis Tarcisio A , Cataneo Daniele C , Cataneo Antônio Jose Maria
Published: July 2019

OBJECTIVES

Our goal was to evaluate, through a systematic review, the efficacy of plasmapheresis in the preoperative preparation of the patient for a thymectomy for the treatment of myasthenia gravis.

METHODS

MEDLINE, Embase, LILACS, Scopus and CENTRAL databases were searched. The following outcomes were evaluated: myasthenic crisis, mortality, pneumonia, bleeding, use of mechanical ventilation, length of hospital stay and intensive care unit (ICU) stay. RevMan 5.3 software provided by the Cochrane Collaboration was used for the meta-analysis.

RESULTS

The total number of patients evaluated in the 7 included studies was 360. Plasmapheresis during the preoperative period did not decrease the myasthenic crisis [risk ratio (RR) 0.36, 95% confidence interval (CI) 0.08–1.66; I2 = 44%; 5 studies, 243 patients]. There was also no change in the mortality rate (RR 0.7, 95% CI 0.11–4.62; I2 = 0%; 3 studies, 172 patients) or pneumonia cases (RR 0.28, 95% CI 0.07–1.09; I2 = 27%; 5 studies, 272 patients). Bleeding was greater in patients who underwent plasmapheresis (mean difference 34.34 ml; 95% CI 24.93–43.75; I2 = 0%). We evaluated the following outcomes: need for mechanical ventilation, hospital stay, ICU stay and mechanical ventilation, but these outcomes were not adequate to perform the meta-analysis due to the high heterogeneity among the studies. Subgroup analysis showed that plasmapheresis performed during the preoperative period in patients with severe disease (Osserman III and IV) decreased the myasthenic crisis postoperatively (RR 0.12, 95% CI 0.02–0.65; I2 = 63%).

CONCLUSIONS

Plasmapheresis may reduce the myasthenic crisis during the postoperative period in patients with severe disease but may produce little or no difference in patients with mild clinical expression of the disease.
Somatic and cerebral near infrared spectroscopy for the monitoring of perfusion during neonatal cardiopulmonary bypass
Authors: Bojan Mirela , Bonaveglio Enrico , Dolcino Andrea , Mirabile Cristian
Published: July 2019

OBJECTIVES

The somatic-cerebral regional oxygen saturation (rSO2) gradient has the potential to reveal a low cardiac output state at an early stage, when systemic vascular resistance increases in order to maintain cerebral perfusion, and results in a drop in somatic rSO2. We hypothesized that during neonatal cardiopulmonary bypass (CPB), the somatic-cerebral rSO2 gradient can also signal poor perfusion, as assessed by an increase in lactate concentration.

METHODS

In a retrospective review of neonatal bypass records, we investigated the association between the somatic-cerebral rSO2 gradient and serial lactate measurements. The somatic-cerebral rSO2 gradient, i.e. the area between the somatic and cerebral rSO2, was calculated for each CPB time interval between 2 lactate measurements, using the trapezoidal method. The association between the somatic-cerebral rSO2 gradient and lactate variation was explored using a mixed model for repeated measurements adjusted for the CPB temperature across intervals.

RESULTS

A total of 94 CPB intervals were analysed in 24 neonates, median age 6 days, median weight 3.1 kg. The median lactate variation per interval was +0.2 mmol l−1 (range −1.5 to +2.7), the median somatic-cerebral gradient was 0 (range −1229% min to +2049% min) and the median CPB temperature was 29.5°C (IQR 28.1–33.4). There was an independent association between the lactate increase and the somatic-cerebral rSO2 gradient (regression coefficient = −0.0006 ± 0.0002, P = 0.009).

CONCLUSIONS

A decrease in the somatic-cerebral rSO2 gradient was associated with an increase in lactate concentration, suggesting that the somatic-cerebral rSO2 gradient is a useful monitoring tool for the adequacy of perfusion during neonatal CPB.
Long-term quality of life in adults following truncus arteriosus repair
Authors: Tay Hilson , Naimo Phillip S , Huang Li , Fricke Tyson A , Brink Johann , d’Udekem Yves , Brizard Christian P , Konstantinov Igor E
Published: July 2019

OBJECTIVES

To date, few studies have assessed the quality of life following congenital cardiac surgery. In this study, we aimed at determining the quality of life after truncus arteriosus (TA) repair using the Short Form 36 questionnaire in adult survivors.

METHODS

Seventy-three patients (age >18 years) who underwent TA repair at the Royal Children’s Hospital, Australia were identified for the study. Of these, 42 patients (58%, 42/73) participated in the study and completed the Short Form 36 questionnaire. The results of the 8 domains and the derived health state summary score (Short Form Six Dimension, SF-6D) were compared with age-matched Australian population controls, and with patients who underwent the arterial switch operation (ASO).

RESULTS

Compared with the age-matched Australian population, 18- to 24-year-old TA patients (31%, 13/42) had lower scores in 6 of 8 domains; 25- to 34-year-old TA patients (36%, 15/42) scored lower in 5 of 8 domains; and 35- to 44-year-old TA patients (33%, 14/42) scored lower in 4 of 8 domains. SF-6D scores were not significantly different between TA patients and the age-matched Australian population. Compared with patients who underwent ASO, 18-to 24-year-old TA patients scored lower in 3 of 8 domains; and 25- to 34-year-old TA patients scored lower in 2 of 8 domains. There was no significant difference in SF-6D scores between TA and patients who underwent the ASO.

CONCLUSIONS

Adult survivors of TA have similar quality of life compared with age-matched Australian controls measured by SF-6D. Despite a higher reoperation rate in TA patients, they have similar quality of life compared with ASO patients.
Ischaemic papillary muscle rupture without significant coronary artery lesion
Authors: Kitada Yuichiro , Arakawa Mamoru , Miyagawa Atsushi , Okamura Homare
Published: July 2019

Papillary muscle rupture is a rare but life-threatening complication of myocardial infarction (MI). Here, we describe a case of papillary muscle rupture caused by a microscopic MI. A 76-year-old woman was referred to our institution, where she developed cardiac arrest upon admission. Severe mitral regurgitation was noted without significant coronary artery lesions. Emergency surgery was performed, and posteromedial papillary muscle rupture was observed. Postoperatively, cardiac magnetic resonance imaging revealed a microscopic MI of the posteromedial papillary muscle.
A Product Formula for Volumes of Divisors Via Okounkov Bodies
Authors: Choi Sung Rak , Jung Seung-Jo , Park Jinhyung , Won Joonyeong
Published: July 2019

We generalize Kawamata’s product formula for volumes of canonical divisors to arbitrary divisors using Okounkov bodies.
Character Ratios for Exceptional Groups of Lie Type
Authors: Liebeck Martin W , Tiep Pham Huu
Published: July 2019

We prove character ratio bounds for finite exceptional groups $G(q)$ of Lie type. These take the form $\dfrac{|\chi (g)|}{\chi (1)} \le \dfrac{c}{q^k}$ for all nontrivial irreducible characters $\chi$ and nonidentity elements $g$, where $c$ is an absolute constant, and $k$ is a positive integer. Applications are given to bounding mixing times for random walks on these groups and also diameters of their McKay graphs.
Transient Immune Activation in BCG-Vaccinated Infant Rhesus Macaques Is Not Sufficient to Influence Oral Simian Immunodeficiency Virus Infection
Authors: Wood Matthew P , Wood Lianna F , Templeton Megan , Fisher Bridget , Lippy Adriana , Jones Chloe I , Lindestam Arlehamn Cecilia S , Sette Alessandro , Fuller James T , Murapa Patience , Jaspan Heather B , Fuller Deborah H , Sodora Donald L
Published: July 2019

BCG vaccination has been demonstrated to increase levels of activated CD4+ T cells, thus potentially influencing mother-to-child transmission of human immunodeficiency virus (HIV). To assess the risk of BCG vaccination in HIV infection, we randomly assigned newborn rhesus macaques to receive BCG vaccine or remain unvaccinated and then undergo oral simian immunodeficiency virus (SIV) challenges 3 weeks later. We observed elevated levels of activated peripheral CD4+ T cells (ie, HLA-DR+CD38+CCR5+ CD4+ T cells) by week 3 after vaccination. BCG was also associated with an altered immune gene expression profile, as well as with monocyte activation in both peripheral blood and the draining axillary lymph node, indicating significant BCG vaccine–induced immune activation. Despite these effects, BCG vaccination did not increase the rate of SIV oral transmission or disease progression. Our findings therefore identify patterns of T-cell and monocyte activation that occur after BCG vaccination but do not support the hypothesis that BCG vaccination is a risk factor for postnatal HIV transmission or increased pathogenesis in infants.
Efficacy of Oral Tenofovir Alafenamide/Emtricitabine Combination or Single-Agent Tenofovir Alafenamide Against Vaginal Simian Human Immunodeficiency Virus Infection in Macaques
Authors: Massud Ivana , Cong Mian-Er , Ruone Susan , Holder Angela , Dinh Chuong , Nishiura Kenji , Khalil George , Pan Yi , Lipscomb Jonathan , Johnson Ryan , Deyounks Frank , Rooney James F , Babusis Darius , Park Yeojin , McCallister Scott , Callebaut Christian , Heneine Walid , García-Lerma J Gerardo
Published: July 2019

Background

Tenofovir alafenamide (TAF)-based regimens are being evaluated for pre-exposure prophylaxis (PrEP). We used a macaque model of repeated exposures to simian human immunodeficiency virus (SHIV) to investigate whether TAF alone or the combination of TAF and emtricitabine (FTC) can prevent vaginal infection.

Methods

Pigtail macaques were exposed vaginally to SHIV162p3 once a week for up to 15 weeks. Animals received clinical doses of FTC/TAF (n = 6) or TAF (n = 9) orally 24 hours before and 2 hours after each weekly virus exposure. Infection was compared with 21 untreated controls.

Results

Five of the 6 animals in the FTC/TAF and 4 of the 9 animals in the TAF alone group were protected against infection (P = .001 and P = .049, respectively). The calculated efficacy of FTC/TAF and TAF was 91% (95% confidence interval [CI], 34.9%–98.8%) and 57.8% (95% CI, −8.7% to 83.6%), respectively. Infection in FTC/TAF but not TAF-treated macaques was delayed relative to controls (P = .005 and P = .114). Median tenofovir diphosphate (TFV-DP) levels in peripheral blood mononuclear cells (PBMCs) were similar among infected and uninfected macaques receiving TAF PrEP (351 and 143 fmols/106 cells, respectively; P = .921).

Conclusions

Emtricitabine/TAF provided a level of protection against vaginal challenge similar to FTC/TFV disoproxil fumarate combination in the macaque model. Our results support the clinical evaluation of FTC/TAF for PrEP in women.
Determination of Cytochrome P450 Isoenzyme 2D6 (CYP2D6) Genotypes and Pharmacogenomic Impact on Primaquine Metabolism in an Active-Duty US Military Population
Authors: Spring Michele D , Sousa Jason C , Li Qigui , Darko Christian A , Morrison Meshell N , Marcsisin Sean R , Mills Kristin T , Potter Brittney M , Paolino Kristopher M , Twomey Patrick S , Moon James E , Tosh Donna M , Cicatelli Susan B , Froude Jeffrey W , Pybus Brandon S , Oliver Thomas G , McCarthy William F , Waters Norman C , Smith Philip L , Reichard Gregory A , Bennett Jason W
Published: July 2019

Background

Plasmodium vivax malaria requires a 2-week course of primaquine (PQ) for radical cure. Evidence suggests that the hepatic isoenzyme cytochrome P450 2D6 (CYP2D6) is the key enzyme required to convert PQ into its active metabolite.

Methods

CYP2D6 genotypes and phenotypes of 550 service personnel were determined, and the pharmacokinetics (PK) of a 30-mg oral dose of PQ was measured in 45 volunteers. Blood and urine samples were collected, with PQ and metabolites were measured using ultraperformance liquid chromatography with mass spectrometry.

Results

Seventy-six CYP2D6 genotypes were characterized for 530 service personnel. Of the 515 personnel for whom a single phenotype was predicted, 58% had a normal metabolizer (NM) phenotype, 35% had an intermediate metabolizer (IM) phenotype, 5% had a poor metabolizer (PM) phenotype, and 2% had an ultrametabolizer phenotype. The median PQ area under the concentration time curve from 0 to ∞ was lower for the NM phenotype as compared to the IM or PM phenotypes. The novel 5,6-ortho-quinone was detected in urine but not plasma from all personnel with the NM phenotype.

Conclusion

The plasma PK profile suggests PQ metabolism is decreased in personnel with the IM or PM phenotypes as compared to those with the NM phenotype. The finding of 5,6-ortho-quinone, the stable surrogate for the unstable 5-hydroxyprimaquine metabolite, almost exclusively in personnel with the NM phenotype, compared with sporadic or no production in those with the IM or PM phenotypes, provides further evidence for the role of CYP2D6 in radical cure.

Clinical Trials Registration

NCT02960568.
A patient and public involvement investigation into healthy eating and weight management advice during pregnancy
Authors: Abayomi J C , Charnley M S , Cassidy L , Mccann M T , Jones J , Wright M , Newson L M
Published: July 2019

Objective

To conduct patient and public involvement (PPI) to gain insight into the experience of healthy eating and weight management advice during pregnancy.

Design

PPI in the planning and development of health interventions, aiming to ensure patient-centred care. Optimum nutrition and weight management are vital for successful pregnancy outcomes, yet many services report poor attendance and engagement.

Setting

Community venues in Liverpool and Ulster (UK).

Participants

Two PPI representatives were involved in all aspects of the study: design, interview questions, recruitment and collection/analysis of feedback.

Intervention

Feedback was collected via note taking during group discussions, two in Liverpool (n = 10 & 5); two in Ulster (n = 7 & 9) and an interview (n = 1, in Ulster).

Main Outcome Measures

Transcript data were collated and thematic analysis was applied in analysis.

Results

Thematic analysis identified three themes: (i) weight gain is inevitable in pregnancy; (ii) healthy eating advice is important but currently lacks consistency and depth and (iii) expectations regarding the type of knowledge/support.

Conclusions

PPI provides opportunity to enhance research design and offers valuable insight towards the needs of healthcare users. Pregnant women want positive health messages, with a focus on what they can/should do, rather than what they should not do. Midwives need to consider their communication with pregnant women, to ensure that their unique relationship is maintained, especially when the topics of diet and weight management are addressed. A well-designed digital intervention could improve access to pregnancy-specific nutrition information; empowering midwives to communicate patient-centred, healthy eating messages with confidence. This has the potential to change dietary and weight management behaviour in pregnant women.