bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for causal links between education and maternal and child health: systematic review
Authors: Mensch Barbara S. , Chuang Erica K. , Melnikas Andrea J. , Psaki Stephanie R.
Published: February 2019

Objective

Numerous studies have documented an inverse association between years of schooling attained, particularly by women, and reduced maternal, infant and child mortality. However, if factors affecting educational attainment — many of which are unobservable, e.g. motivation and genetic endowment — also affect the likelihood of engaging in behaviours that enhance health, then assumed effects of schooling will be inflated in analyses that do not address this endogeneity. This systematic review assesses evidence for a causal link between education and maternal and child health in low and middle‐income countries.

Methods

Eligible studies controlled for observable and unobservable factors affecting both education and health. Reported effects were converted into partial correlations. When possible, we also conducted meta‐analyses to estimate mean effects by outcome.

Results

Of 4952 papers identified, 16 met the inclusion criteria. The 15 child health papers examined neonatal, infant and child mortality, stunting and wasting. Significant effects of education on infant and child health were observed for 30 of 33 models that did not account for endogeneity. In contrast, only 18 of 46 effects were significant in models that addressed endogeneity. Notably, for only one outcome —child mortality measured dichotomously —was the effect of maternal educational attainment significant in a meta‐analysis. The one maternal morbidity paper found significant effects for the two preventable outcomes considered.

Conclusion

While we find evidence for a causal link between education and health, effects are weaker in models that address endogeneity compared to naïve models that do not account for unobservable factors affecting both education and health. Advances in women's educational outcomes have undoubtedly played a role in improving health in many settings; however, the effect is not as strong as some researchers and advocates have claimed.
Effect of a maternal and newborn health system quality improvement project on the use of facilities for childbirth: a cluster‐randomised study in rural Tanzania
Authors: Larson Elysia , Gage Anna D. , Mbaruku Godfrey M. , Mbatia Redempta , Haneuse Sebastien , Kruk Margaret E.
Published: February 2019

Objectives

Reduction in maternal and newborn mortality requires that women deliver in high quality health facilities. However, many facilities provide sub‐optimal quality of care, which may be a reason for less than universal facility utilisation. We assessed the impact of a quality improvement project on facility utilisation for childbirth.

Methods

In this cluster‐randomised experiment in four rural districts in Tanzania, 12 primary care clinics and their catchment areas received a quality improvement intervention consisting of in‐service training, mentoring and supportive supervision, infrastructure support, and peer outreach, while 12 facilities and their catchment areas functioned as controls. We conducted a census of all deliveries within the catchment area and used difference‐in‐differences analysis to determine the intervention's effect on facility utilisation for childbirth. We conducted a secondary analysis of utilisation among women whose prior delivery was at home. We further investigated mechanisms for increased facility utilisation.

Results

The intervention led to an increase in facility births of 6.7 percentage points from a baseline of 72% (95% Confidence Interval: 0.6, 12.8). The intervention increased facility delivery among women with past home deliveries by 18.3 percentage points (95% CI: 10.1, 26.6). Antenatal quality increased in intervention facilities with providers performing an additional 0.5 actions across the full population and 0.8 actions for the home delivery subgroup.

Conclusions

We attribute the increased use of facilities to better antenatal quality. This increased utilisation would lead to lower maternal mortality only in the presence of improvement in care quality.
Tumour necrosis factor‐related apoptosis‐inducing ligand induces apoptosis in canine hemangiosarcoma cells in vitro
Authors: Goto Minami , Owaki Keishi , Hirata Akihiro , Yanai Tokuma , Sakai Hiroki
Published: February 2019

Tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) is an apoptosis‐inducing cytokine that shows potential therapeutic value for human neoplasms, and is effective in some canine tumours; however, its potential for killing canine hemangiosarcoma (HSA) cells is unknown. Thus, we evaluated the proapoptotic effect of TRAIL in nine canine HSA cell lines. Cells (JuA1, JuB2, JuB2‐1, JuB4, Re11, Re12, Re21, Ud2 and Ud6) were cultured with three recombinant human TRAILs (rhTRAILs): TRAIL‐TEC derived fromEscherichia coli, TRAIL‐TL derived from mammalian cells and isoleucine zipper recombinant human TRAIL (izTRAIL) containing an isoleucine‐zippered structure that facilitates trimerization. TRAIL‐TEC did not decrease the cell viability in any of the cell lines tested, whereas the other two rhTRAILs effectively decreased the viability of all cell lines as assessed by the WST‐1 assay. In canine HSA cells, izTRAIL induced apoptosis more effectively than TRAIL‐TL. In JuB4, Re12, and Ud6 cells, izTRAIL increased the activation of caspase‐3 and caspase‐8 and caused poly (ADP‐ribose) polymerase degradation. Moreover, izTRAIL treatment increased the proportion of Annexin V+/ Propidium iodide (PI)− apoptotic cells and nuclear fragmentation in izTRAIL‐sensitive cells. These results show that rhTRAIL can induce apoptosis in canine HSA cells, but the sensitivity of TRAIL was different depending on the cell lines. Therefore, TRAIL could be an effective therapeutic agent against canine HSA, but the specific mechanism of resistance should be determined to clarify under what conditions this treatment would be most effective.
Effect of three resuscitative fluid therapy strategies on NT‐proBNP concentration in healthy dogs
Authors: Khoo Alison , Waldner Cheryl L. , Carr Anthony P. , Gaunt M. Casey
Published: February 2019

Objective

To determine if 3 resuscitative fluid therapy strategies increase N‐terminal pro‐brain natriuretic peptide (NT proBNP) levels in healthy dogs.

Design

Randomized crossover trial.

Setting

Veterinary teaching hospital.

Animals

Plasma NT proBNP concentrations were measured in 6 healthy purpose‐bred dogs that received 3 resuscitative fluid therapy protocols.

Measurements and main results

Crystalloid, synthetic colloid, or hypertonic saline fluids were administered at resuscitative doses. Blood samples were collected via an indwelling catheter before, and at set time points between 0.5 and 36 h after fluid therapy and analyzed for NT‐proBNP. A general linear mixed model was used to estimate the differences in NT‐proBNP over time and among treatments. None of the resuscitative fluid therapy protocols caused increases of serum NT‐proBNP beyond the previously reported cutoff concentration used to differentiate cardiac versus noncardiac causes of respiratory signs. Dogs receiving crystalloid fluid therapy had the most significant and prolonged increase in serum NT‐proBNP concentration above baseline compared to dogs receiving either resuscitative doses of colloids or hypertonic saline.

Conclusions

Serum NT‐proBNP concentration in normal dogs was not increased beyond concentrations previously established to equate to cardiac disease after receiving resuscitative fluid therapy with either a balanced crystalloid solution, hypertonic saline, or a synthetic colloid solution in this study.
Comparison of pentobarbital‐phenytoin alone vs propofol prior to pentobarbital‐phenytoin for euthanasia in 436 client‐owned dogs
Authors: Bullock Jessica M. , Lanaux Travis M. , Shmalberg Justin W.
Published: February 2019

Objective

To report the incidence of adverse events during euthanasia of client‐owned dogs administered either intravenous pentobarbital/phenytoin (PP) or PP after propofol delivery.

Design/Setting

Prospective, observational, multi‐site study.

Animals

Four hundred thirty‐six dogs undergoing client‐elected euthanasia over a 1‐year period.

Interventions

Interventions included placement of an IV catheter and delivery of euthanasia agents (PP for the PP group, propofol followed by PP for the propofol group). Seven pre‐determined adverse events were recorded: agonal breaths, urination, defecation, vocalization, muscle activity, dysphoria, and catheter complications. Euthanasia scores for each patient were defined as the sum of all adverse events (0–7) the patient exhibited.

Measurements and Main Results

Two hundred thirty‐six dogs were in the PP group and 200 dogs were in the propofol group. No significant differences were detected in the dose of PP administered (166.9 ± 105.6 mg/kg for PP group, 182.6 ± 109.8 mg/kg for propofol group). Propofol dogs received 4.5 ± 2.9 mg/kg propofol. The incidence of ≥ 1 adverse event was 35.2% in the PP group and 26.5% in the propofol group (P= 0.052). Mean euthanasia scores (0.47 PP group, 0.32 propofol group) were not significantly different (P= 0.08). Propofol significantly reduced the incidence of muscle activity (6% vs. 14%, odds ratio 0.39;P= 0.0079).

Conclusions

There was no difference in the likelihood of the studied adverse events during client‐elected euthanasia in dogs when propofol was used prior to PP. There was a significant reduction in perimortem muscle activity if propofol was given prior to PP.
Evaluation of biomarkers of kidney injury following 4% succinylated gelatin and 6% hydroxyethyl starch 130/0.4 administration in a canine hemorrhagic shock model
Authors: Boyd Corrin J. , Claus Melissa A. , Raisis Anthea L. , Cianciolo Rachel , Bosio Erika , Hosgood Giselle , Nabity Mary , Mori Trevor , Barden Anne , Sharp Claire R. , Smart Lisa
Published: February 2019

Objective: To investigate the association between synthetic colloids and biomarkers of acute kidney injury (AKI) in dogs with hemorrhagic shock.

Design: Experimental interventional study.

Setting: University.

Animals: Twenty‐four healthy ex‐racing Greyhounds.

Interventions: Anesthetized Greyhounds subjected to hemorrhage for 60 min were resuscitated with 20 mL/kg of fresh whole blood (FWB), 6% hydroxyethyl starch (HES) 130/0.4, 4% succinylated gelatin (GELO), or 80 mL/kg of isotonic crystalloid (CRYST) over 20 min (n = 6 per treatment). Concentrations of biomarkers of AKI were measured at baseline, end of hemorrhage, and at 40 (T60), 100 (T120), and 160 (T180) min after fluid bolus. Biomarkers included neutrophil gelatinase‐associated lipocalin in urine and serum (uNGAL; sNGAL), and urine cystatin C (uCYSC), kidney injury molecule‐1 (uKIM), clusterin (uCLUST), osteopontin, gamma‐glutamyl transferase, monocyte chemoattractant protein‐1 (uMCP), interleukin‐6, interleukin‐8, protein (uPROT), hyaluronan, and F2‐isoprostanes. Renal histology was scored for tubular injury and microvesiculation. Biomarker fold‐change from baseline was compared between groups using mixed effects models (Bonferroni–Holm corrected P<0.05). Frequencies of histology scores were compared by Fisher's exact test.

Measurements and main results: In dogs treated with GELO, uNGAL fold‐change was markedly greater compared with all other groups at T60, T120, and T180 (all P<0.001), and uCYSC was greater at T60 compared with CRYST (P<0.001), and at T120 and T180 compared with all other groups (all P<0.001). Smaller, albeit significant, between‐group differences in uKIM, uCLUST, uMCP, and urine protein concentration were observed across the FWB, GELO, and HES groups, compared with CRYST. The GELO group more frequently had marked tubular microvesiculation than the other groups (P = 0.015) although tubular injury scores were comparable.

Conclusion: In dogs with hemorrhagic shock, GELO was associated with greater magnitude increases in urine biomarkers of AKI and more frequent marked tubular microvesiculation, compared with FWB, CRYST, and HES.
Stifle joint osteoarthritis at the time of diagnosis of cranial cruciate ligament injury is higher in Boxers and in dogs weighing more than 35 kilograms
Authors: Gilbert Samuel , Langenbach Anke , Marcellin‐Little Denis J. , Pease Anthony P. , Ru Hongyu
Published: February 2019

Osteoarthritis is a ubiquitous disease in dogs. The purpose of this retrospective study was to characterize the severity and distribution of osteoarthritis (OA) within the joint and to identify differences among dog breeds in the severity of OA in the cranial cruciate ligament (CCL)‐deficient stifle joint. Radiographs of 240 stifles from 51 Boxers, 66 German Shepherds, 100 Labrador Retrievers, and 23 Siberian Huskies with confirmed CCL rupture were included. Radiographs of the stifle joint were evaluated and OA severity was graded at 33 sites within and around the joint, and patella alta was graded as present or absent for a potential total stifle OA score of 100. Osteophyte size was correlated to OA severity score. Total OA scores were calculated and compared within and between breeds globally as well as at each joint site. Dogs weighing >35 kg had a higher total OA score than those weighing <35 kg. Osteoarthritis scores were highest at the apical patella, proximolateral tibia, and sesamoid bones, corresponding to the proximal, lateral, and caudal aspects of the joint, respectively. No statistically significant differences were found among the mean OA scores of various stifle joint regions. Boxer dogs had a higher total OA score than other breeds. We concluded that dogs have a consistent distribution pattern of OA within the stifle joint after CCL injury. Radiographic OA is more severe in the proximal, lateral, and caudal aspects of the joint. Boxers had more severe OA than the other breeds evaluated in the study.
Gut microbiota diversity is associated with cardiorespiratory fitness in post‐primary treatment breast cancer survivors
Authors: Carter Stephen J. , Hunter Gary R. , Blackston J. Walker , Liu Nianjun , Lefkowitz Elliot J. , Van Der Pol William J. , Morrow Casey D. , Paulsen Jesseca A. , Rogers Laura Q.
Published: February 2019

New Findings

What is the central question of this study?

Does the link between cardiorespiratory fitness and gut microbiota diversity persist after adjusting for the potential effects of percentage body fat and activity‐related energy expenditure (AEE)?

What is the main finding and its importance?

This is the first study to examine the link between cardiorespiratory fitness and gut microbiota diversity while accounting for the underlying effects of percentage body fat and free‐living AEE. Results from the present work suggest that cardiorespiratory fitness, not physical activity, is a superior correlate of gut microbiota diversity among post‐primary treatment, non‐metastatic breast cancer survivors.

Cancer treatment uniquely triggers multiple physiological shifts detrimental to overall health. Although previous research indicates a link between the gut microbiota and cardiorespiratory fitness, it is unclear whether these findings are attributable to potential underlying effects of percentage body fat or free‐living activity energy expenditure (AEE). The microbe composition of faecal specimens from 37 breast cancer survivors was determined using 16S microbiome analyses. Individual‐sample microbiota diversity (α‐diversity) and between‐sample community differences (β‐diversity) were examined. Peak oxygen uptake () was estimated from a graded exercise test consistent with the modified Naughton protocol, in which exercise terminates at 85% of age‐predicted maximal heart rate. The AEE was measured over 10 days using doubly labelled water, wherein the percentage body fat was calculated from total body water. Pearson correlations revealed α‐diversity indices (Chao1, observed species, PD whole tree and Shannon) to be positively associated with (r = 0.34–0.51; P < 0.05), whereas the percentage of maximal heart rate during stages 1–4 of the graded exercise test (r = −0.34 to −0.50; P < 0.05) and percentage body fat (r = −0.32 to −0.41; P < 0.05) were negatively associated with the same α‐diversity indices. Multiple linear regression models showed that accounted for 22 and 26% of the variance in taxonomic richness (observed species) and phylogenic diversity after adjustment for percentage body fat and menopausal status. Unweighted UniFrac (β‐diversity) was significant for several outcomes involving cardiorespiratory fitness, and significant taxa comparisons were found. Associations between gut microbiota and free‐living AEE were not found. Results from the present work suggest that cardiorespiratory fitness, not physical activity, is a superior correlate of gut microbiota diversity.
Mapping of ocean currents in shallow water using moving ship acoustic tomography
Authors: Huang Chen-Fen , Li Yun-Wen , Taniguchi Naokazu
Published: February 2019

This study investigates techniques for the acoustic mapping of ocean currents in a shallow-water environment using moored and ship-towed stations. The currents are estimated using the differential travel times (DTTs) observed in the reciprocal acoustic transmissions between those stations. Due to the relative motion induced by the ship-towed station, the Doppler shift estimated from the measured channel impulse response is used to compensate for the arrival patterns and to correct the influence of the relative speed on the DTTs. Furthermore, to estimate the DTTs from the arrival patterns received in the reciprocal directions, a method is devised which involves the time-evolving cross-correlation function of the reciprocal arrival patterns. A feasibility test was carried out at Sizhiwan Marine Test Field, Kaohsiung, Taiwan in September of 2015. The currents were estimated using the data collected from one ship-towed and four moored stations. The estimated currents are consistent with the direct measurements from a shipboard acoustic Doppler current profiler and reveal the spatial distribution of the currents.
In India, Hindu pride boosts pseudoscience
Authors: Kumar Sanjay
Published: February 2019

Claims of great technological achievements in ancient times trigger ridicule and concern.
Heterochromatin anomalies and double-stranded RNA accumulation underlie
C9orf72
poly(PR) toxicity
Authors: Zhang Yong-Jie , Guo Lin , Gonzales Patrick K. , Gendron Tania F. , Wu Yanwei , Jansen-West Karen , O’Raw Aliesha D. , Pickles Sarah R. , Prudencio Mercedes , Carlomagno Yari , Gachechiladze Mariam A. , Ludwig Connor , Tian Ruilin , Chew Jeannie , DeTure Michael , Lin Wen-Lang , Tong Jimei , Daughrity Lillian M. , Yue Mei , Song Yuping , Andersen Jonathan W. , Castanedes-Casey Monica , Kurti Aishe , Datta Abhishek , Antognetti Giovanna , McCampbell Alexander , Rademakers Rosa , Oskarsson Björn , Dickson Dennis W. , Kampmann Martin , Ward Michael E. , Fryer John D. , Link Christopher D. , Shorter James , Petrucelli Leonard
Published: February 2019

How dipeptide repeats cause pathology

A repeat expansion in the chromosome 9 open reading frame 72 (
C9orf72
) gene is the most common known cause of two neurodegenerative diseases: frontotemporal dementia and amyotrophic lateral sclerosis. This expansion leads to the abnormal production of proteins of repeating dipeptides, but their contribution to disease pathogenesis remains unclear. Zhang
et al.
engineered a mouse model to study the consequences of one of these dipeptides—prolinearginine dipeptide repeat protein, poly(PR)—in the brain. They found that poly(PR) caused neuron loss as well as motor and memory impairments. These detrimental effects resulted from poly(PR)-induced perturbation of heterochromatin function, a tightly packed form of DNA that represses gene expression.

Science
, this issue p.
eaav2606
Density fluctuations as door-opener for diffusion on crowded surfaces
Authors: Henß Ann-Kathrin , Sakong Sung , Messer Philipp K. , Wiechers Joachim , Schuster Rolf , Lamb Don C. , Groß Axel , Wintterlin Joost
Published: February 2019

A path through a crowd

Catalytic reactions on surfaces occur at pressures at which the surfaces are completely covered with adsorbed molecules. It would seem that this arrangement would interfere with reactants encountering one another through diffusion processes. Henß
et al.
used high-speed scanning tunneling microscopy to follow the diffusion of oxygen atoms on a ruthenium surface that was fully covered with carbon monoxide (CO) molecules (see the Perspective by Magnussen). Oxygen-atom diffusion was unexpectedly fast. A theoretical model revealed that CO diffusion appears to open pathways for oxygen-atom movement.

Science
, this issue p.
715
; see also p.
695
Double-negative-index ceramic aerogels for thermal superinsulation
Authors: Xu Xiang , Zhang Qiangqiang , Hao Menglong , Hu Yuan , Lin Zhaoyang , Peng Lele , Wang Tao , Ren Xuexin , Wang Chen , Zhao Zipeng , Wan Chengzhang , Fei Huilong , Wang Lei , Zhu Jian , Sun Hongtao , Chen Wenli , Du Tao , Deng Biwei , Cheng Gary J. , Shakir Imran , Dames Chris , Fisher Timothy S. , Zhang Xiang , Li Hui , Huang Yu , Duan Xiangfeng
Published: February 2019

Elastic ceramics

Aerogels hold promise as lightweight replacements for thermal insulation. However, poor mechanical stability has hampered progress in moving toward commercialization. Xu
et al.
designed a mechanical metamaterial that pinches in a small amount when you compress it (see the Perspective by Chhowalla and Jariwala). This is characteristic of materials with a negative Poisson's ratio and dramatically improves mechanical stability. The trick was using three-dimensional graphene structures to template the ceramic aerogels, thus producing a superinsulating material endowed with excellent mechanical properties.

Science
, this issue p.
723
; see also p.
694
Structures of human Na
v
1.7 channel in complex with auxiliary subunits and animal toxins
Authors: Shen Huaizong , Liu Dongliang , Wu Kun , Lei Jianlin , Yan Nieng
Published: February 2019

Targeting sodium channels

Voltage-gated sodium (Na
v
) channels have been implicated in cardiac and neurological disorders. There are many subtypes of these channels, making it challenging to develop specific therapeutics. A core α subunit is sufficient for voltage sensing and ion conductance, but function is modulated by β subunits and by natural toxins that can either act as pore blockers or gating modifiers (see the Perspective by Chowdhury and Chanda). Shen
et al.
present the structures of Na
v
1.7 in complex with both β1 and β2 subunits and with animal toxins. Pan
et al.
present the structure of Na
v
1.2 bound to β2 and a toxic peptide, the µ-conotoxin KIIIA. The structure shows why KIIIA is specific for Na
v
1.2. These and other recently determined Na
v
structures provide a framework for targeted drug development.

Science
, this issue p.
1303
, p.
1309
; see also p.
1278
Earth's rugged lower mantle
Authors: Houser Christine
Published: February 2019

Seismic data reveal kilometer-scale topography of the lower-mantle boundary
Revealing a microbial carcinogen
Authors: Bleich Rachel M. , Arthur Janelle C.
Published: February 2019

An
E. coli
–derived colibactin-DNA adduct is detected in intestinal tissues
Conservation and conflict
The Snow Leopard Project
Alex Dehgan
PublicAffairs, 2019. 288 pp.
Authors: Cooney Rosie , Karimov Khalil
Published: February 2019

Afghanistan's rich natural heritage shines in an insider's account of the foundings of its first national parks
Keep science on the horizon
Authors: Beddington John
Published: February 2019

Science is a global endeavor that affects well-being and stability on many fronts, so anything that damages the scientific enterprise in one country, particularly a powerhouse that is internationally networked, damages conditions everywhere. As the United Kingdom tumbles toward the 29 March Brexit deadline, the world should feel uneasy, at the very least. Paradoxically, science has never been high on the Brexit agenda likely because there is general agreement among politicians on all sides that good science relations are in everyone's best interest. Thus, the United Kingdom does not have a plan in place for preserving science. Everyone who cares about the future of science needs to continue to make the case for the smoothest transition on 29 March—whether there is a deal or not—so that U.K. science and global science do not become accidental victims.
Key Physiology of a Nitrite-Dependent Methane-Oxidizing Enrichment Culture
Authors: Guerrero-Cruz Simon , Stultiens Karin , van Kessel Maartje A. H. J. , Versantvoort Wouter , Jetten Mike S. M. , Op den Camp Huub J. M. , Kartal Boran
Published: February 2019

Methane is an important greenhouse gas with a radiative forcing 28 times that of carbon dioxide over a 100-year time scale. The emission of methane to the atmosphere is controlled by aerobic and anaerobic methanotrophs, which are microorganisms that are able to oxidize methane to conserve energy. While aerobic methanotrophs have been studied for over a century, knowledge on the physiological characteristics of anaerobic methanotrophs is scarce. Here, we describe kinetic properties of “
Candidatus
Methylomirabilis lanthanidiphila,” a nitrite-dependent methane-oxidizing microorganism, which is ecologically important and can be applied in wastewater treatment.
Antimicrobial Particle-Based Novel Sanitizer for Enhanced Decontamination of Fresh Produce
Authors: Huang Kang , Nitin Nitin
Published: February 2019

The limitation of current sanitation processes for inactivation of microbes on the surfaces of fresh produce is due to nonspecific consumption of sanitizers by reactions with the food matrix and complexity of surface chemistries and structural features of produce surfaces. This study demonstrates a novel approach to enhance sanitation effectiveness of fresh produce using a particle-based sanitizer. The particle-based sanitizer concept provides localized high concentration delivery of chlorine to the surfaces of fresh produce and enables more than 5 logs of inactivation of inoculated bacteria on fresh produce surfaces without significant changes in produce quality. The results of this study illustrate the potential of this approach to address the unmet need for improving sanitation of fresh produce. Further validation of this approach using a scaled-up produce washing system will enable commercialization of this novel concept.
Structure-Function Analysis Indicates that an Active-Site Water Molecule Participates in Dimethylsulfoniopropionate Cleavage by DddK
Authors: Peng Ming , Chen Xiu-Lan , Zhang Dian , Wang Xiu-Juan , Wang Ning , Wang Peng , Todd Jonathan D. , Zhang Yu-Zhong , Li Chun-Yang
Published: February 2019

The climate-active gas dimethyl sulfide (DMS) plays an important role in global sulfur cycling and atmospheric chemistry. DMS is mainly produced through the bacterial cleavage of marine dimethylsulfoniopropionate (DMSP). When released into the atmosphere from the oceans, DMS can be photochemically oxidized into DMSO or sulfate aerosols, which form cloud condensation nuclei that influence the reflectivity of clouds and, thereby, global temperature. SAR11 bacteria are the most abundant marine heterotrophic bacteria, and many of them contain DMSP lyase DddK to cleave DMSP, generating DMS. In this study, based on structural analyses and mutational assays, we revealed the catalytic mechanism of DddK, which has universal significance in SAR11 bacteria. This study provides new insights into the catalytic mechanism of DddK, leading to a better understanding of how SAR11 bacteria generate DMS.
Group AStreptococcus-Mediated Host Cell Signaling
Authors: Pancholi Vijay
Published: February 2019

In the past decade, the field of the cellular microbiology of group AStreptococcus(S. pyogenes) infection has made tremendous advances and touched upon several important aspects of pathogenesis, including receptor biology, invasive and evasive phenomena, inflammasome activation, strain-specific autophagic bacterial killing, and virulence factor-mediated programmed cell death. The noteworthy aspect ofS. pyogenes-mediated cell signaling is the recognition of the role of M protein in a variety of signaling events, starting with the targeting of specific receptors on the cell surface and on through the induction and evasion of NETosis, inflammasome, and autophagy/xenophagy to pyroptosis and apoptosis. Variations in reports onS. pyogenes-mediated signaling events highlight the complex mechanism of pathogenesis and underscore the importance of the host cell andS. pyogenesstrain specificity, as well asin vitro/in vivoexperimental parameters. The severity ofS. pyogenesinfection is, therefore, dependent on the virulence gene expression repertoire in the host environment and on host-specific dynamic signaling events in response to infection. Commonly known as an extracellular pathogen,S. pyogenesfinds host macrophages as safe havens wherein it survives and even multiplies. The fact that endothelial cells are inherently deficient in autophagic machinery compared to epithelial cells and macrophages underscores the invasive nature ofS. pyogenesand its ability to cause severe systemic diseases.S. pyogenesis still one of the top 10 causes of infectious mortality. Understanding the orchestration of dynamic host signaling networks will provide a better understanding of the increasingly complex mechanism ofS. pyogenesdiseases and novel ways of therapeutically intervening to thwart severe and often fatal infections.
Bacteroidetes
Gliding Motility and the Type IX Secretion System
Authors: McBride Mark J.
Published: February 2019

Members of the phylum
Bacteroidetes
have many unique features, including gliding motility and the type IX protein secretion system (T9SS).
Bacteroidetes
gliding and T9SSs are common in, but apparently confined to, this phylum. Most, but not all, members of the phylum secrete proteins using the T9SS, and most also exhibit gliding motility. T9SSs secrete cell surface components of the gliding motility machinery and also secrete many extracellular or cell surface enzymes, adhesins, and virulence factors. The components of the T9SS are novel and are unrelated to those of other bacterial secretion systems. Proteins secreted by the T9SS rely on the Sec system to cross the cytoplasmic membrane, and they use the T9SS for delivery across the outer membrane. Secreted proteins typically have conserved C-terminal domains that target them to the T9SS. Some of the T9SS components were initially identified as proteins required for gliding motility. Gliding does not involve flagella or pili and instead relies on the rapid movement of motility adhesins, such as SprB, along the cell surface by the gliding motor. Contact of the adhesins with the substratum provides the traction that results in cell movement. SprB and other motility adhesins are delivered to the cell surface by the T9SS. Gliding and the T9SS appear to be intertwined, and components of the T9SS that span the cytoplasmic membrane may energize both gliding and protein secretion. The functions of the individual proteins in each process are the subject of ongoing investigations.
U-Pb and oxygen isotope characteristics of Timanian- and Caledonian-age detrital zircons from the Brooks Range, Arctic Alaska, USA
Authors: Robinson F.A. , Toro J. , Pease V.
Published: February 2019

The Devonian connection between the Brooks Range of Alaska, USA, with the continental margin of Arctic Canada and its subsequent Jurassic–Cretaceous counterclockwise rotation to form the Amerasian Basin, is a highly debated topic in Arctic tectonics. This resource-rich region was assembled from terranes that formed part of Laurentia or Baltica, or were juvenile oceanic arcs in the early Paleozoic that were brought together during Caledonian Orogenesis and the subsequent collision that formed Pangea (Uralide Orogeny). Elements of these orogens, as well as older ones, are predicted to occur in the Brooks Range of Arctic Alaska. This study presents the first combined zircon U-Pb and oxygen data from six Brooks Range metasedimentary units with assumed Neoproterozoic to Devonian ages. Three distinct detrital zircon patterns are identified in these units: (1) those with Neoproterozoic maximum depositional ages characteristic of the Timanide Orogen of northern Baltica and adjacent parts of Siberia, (2) an almost unimodal Siluro–Ordovician (443.5 ± 2.3 Ma) detrital zircon population consistent with the oceanic Apoon arc believed to have existed off shore of northern Laurentia and to have accreted to the North Slope subterrane during the Caledonian event, and (3) those with Middle Devonian maximum depositional ages consistent with post-accretion extension during the final (Scandian) phase of Caledonian Orogenesis. Oxygen isotopes from the same zircons reveal minor to significant crustal contamination with approximately two thirds (n = 255/405) having δ18O values >5.9‰ (above the mantle field of 5.3 ± 0.6‰). Pattern 1 units exhibit a progressive increase in δ18O values throughout the Proterozoic (5.99 to 9.29‰) indicative of increasing crustal growth and Timanide age zircons yield average δ18O values of 7.18 ± 0.64‰ (n = 26) suggestive of more crustal influence than Caledonian age zircons, possibly reflecting northern Baltica signatures. The unimodal population in Pattern 2 yields average δ18O values of 5.49 ± 0.66‰ (n = 17) and 6.02 ± 0.27‰ (n = 23) prior to and during, respectively, the main Caledonian event and suggest derivation from Devonian juvenile arc sources possibly representing the initiation of the collision between Laurentia and Baltica. Similar to Pattern 1, the δ18O values associated with Pattern 3 show a progressive increase in δ18O values throughout the Proterozoic (5.00 to 9.39‰). However, Pattern 3 also exhibits a distinct juvenile fingerprint (6.13 ± 0.24‰, n = 51) during the main Caledonian event and a slight increase to 7.12 ± 1‰ (n = 7) in post-Caledonian zircons possibly suggest correlating with a post-accretion phase in which proximally sourced zircon-bearing detritus was deposited in extension-related basins marking the joining of Laurentia and Baltica.
Treatment of neurotrophic keratopathy with minimally invasive corneal neurotisation: long-term clinical outcomes and evidence of corneal reinnervation
Authors: Catapano Joseph , Fung Simon S M , Halliday William , Jobst Cecilia , Cheyne Douglas , Ho Emily S , Zuker Ronald M , Borschel Gregory H , Ali Asim
Published: February 2019

Aim

To report clinical outcomes and evidence of corneal innervation in patients with neurotrophic keratopathy (NK) treated with minimally invasive corneal neurotisation (MICN) using a sural nerve graft and donor sensory nerves from the face.

Methods

Patients undergoing MICN at The Hospital for Sick Children, Toronto, Canada were prospectively recruited. Data on central corneal sensation (CCS, measured with Cochet-Bonnet aesthesiometer), best-corrected visual acuity (BCVA) and corneal epithelial integrity were collected. In four patients who subsequently underwent keratoplasty, immunohistochemical analysis was performed on the corneal explants. One patient underwent magnetoencephalography (MEG) after MICN to characterise the neurophysiological pathways involved.

Results

Between November 2012 and February 2017, 19 eyes of 16 patients underwent MICN. Mean follow-up was 24.0±16.1 months (range, 6–53). Mean CCS significantly improved from 0.8±2.5 mm to 49.7±15.5 mm at final follow-up (p<0.001). Mean BCVA remained stable, and the number of episodes of corneal epithelial defects after MICN was significantly reduced compared with the year leading up to the procedure (21% vs 89%, respectively; p<0.0001). In the four eyes that underwent keratoplasties after MICN, all transplants fully re-epithelialised and regained sensation subsequently. Immunohistochemistry of the corneal explants demonstrated evidence of corneal reinnervation. In one patient who was 8 months after MICN, novel neuroactivity was detected on MEG in the ipsilateral somatosensory cortex on mechanical stimulation of the reinnervated cornea.

Conclusions

By providing an alternative source of innervation, MICN improves corneal sensation and stabilises the corneal epithelium, permitting optical keratoplasty for patients with NK-related corneal opacity.
Decreased contrast sensitivity at high altitude
Authors: Gekeler Katrin , Schatz Andreas , Fischer Manuel Dominik , Schommer Kai , Boden Katrin , Bartz-Schmidt Karl Ulrich , Gekeler Florian , Willmann Gabriel
Published: February 2019

Background/aims

The aim of this study was to investigate a change in visual acuity and contrast sensitivity (CS) during high altitude exposure in healthy subjects due to the effects of hypobaric hypoxia. This study is related to the Tübingen High Altitude Ophthalmology study.

Methods

Visual acuity and Weber CS were tested monocularly using the Freiburger Visual Acuity and Contrast Test under standardised conditions in 14 healthy subjects at high altitude at the Capanna Margherita (4559 m, Italy) and compared with baseline measurements in Tübingen (341 m, Germany). Intraindividual differences between baseline and follow-up examinations were calculated by multivariate analysis of variance for repeated measures. Clinical parameters of peripheral oxygen saturation (SpO2) and heart rate (HR) as well as scores for acute mountain sickness (AMS) were correlated to psychophysical tests by Pearson’s correlation coefficient.

Results

A significant decrease in CS with a mean effect size of −0.13 logCS was found for Weber CS (day 1=−0.16±0.22, p=0.01; day 2=−0.10±0.2, p=0.049; day 3=−0.12±0.19, p=0.03) at high altitude compared with baseline. Visual acuity remained unchanged. Decreased CS correlated with SpO2 (r=0.53, p=0.046) but not with HR (r=− 0.16, p=0.59) and occurred irrespective of AMS at high altitude.

Conclusion

High altitude exposure leads to decreased CS. Changes occur independent of AMS. This finding is of clinical importance to trekkers and mountaineers exposed to high altitude as visual processing in particular under mesopic conditions at dusk and dawn is altered. Furthermore, it provides novel insight into hypoxia related changes in CS function.
Philadelphia Telemedicine Glaucoma Detection and Follow-up Study: confirmation between eye screening and comprehensive eye examination diagnoses
Authors: Hark Lisa A , Myers Jonathan S , Ines Andrew , Jiang Alicia , Rahmatnejad Kamran , Zhan Tingting , Leiby Benjamin E , Hegarty Sarah , Fudemberg Scott J , Mantravadi Anand V , Waisbourd Michael , Henderer Jeffrey D , Burns Christine , Divers Meskerem , Molineaux Jeanne , Pizzi Laura T , Murchison Ann P , Saaddine Jinan , Pasquale Louis R , Haller Julia A , Katz L Jay
Published: February 2019

Aims

To evaluate agreement between ocular findings of a telemedicine eye screening (visit 1) with diagnoses of a comprehensive eye examination (visit 2).

Methods

A primary care practice (PCP)–based telemedicine screening programme incorporating fundus photography, intraocular pressure (IOP) and clinical information was conducted. Eligible individuals were African American, Hispanic/Latino or Asian over the age of 40; Caucasian individuals over age 65; and adults of any ethnicity over age 40 with a family history of glaucoma or diabetes. Participants with abnormal images or elevated IOP were invited back for a complete eye examination. Both visit 1 and visit 2 were conducted at participants’ local PCP. Ocular findings at visit 1 and eye examination diagnoses at visit 2 are presented, including a cost analysis.

Results

Of 906 participants who attended visit 1, 536 were invited to visit 2 due to ocular findings or unreadable images. Among the 347 (64.9%) who attended visit 2, 280 (80.7%) were diagnosed with at least one ocular condition. Participants were predominately women (59.9%) and African American (65.6%), with a mean age (±SD) of 60.6±11.0 years. A high diagnostic confirmation rate (86.0%) was found between visit 1 and visit 2 for any ocular finding. Of 183 with suspicious nerves at visit 1, 143 (78.1%) were diagnosed as glaucoma or glaucoma suspects at visit 2.

Conclusions

This screening model may be adapted and scaled nationally and internationally. Referral to an ophthalmologist is warranted if abnormal or unreadable fundus images are detected or IOP is >21 mm Hg.

Trial registration number

NCT02390245.
Arterial flow patterns in healthy transitioning near-term neonates
Authors: Stritzke Amelie , Murthy Prashanth , Kaur Sharandeep , Kuret Verena , Liang Zhiying , Howell Sarah , Tyberg John V
Published: February 2019

Objective

Significant haemodynamic changes occur at delivery impacting organ blood flow distribution. We aimed to characterise Doppler indices patterns over time in three different organs (brain, gut and kidney) and test them as measures of vascular resistance.

Design

Observational cohort study. Serial Doppler interrogations of the anterior cerebral, superior mesenteric and renal arteries within 2 hours, 2–6, and 24 hours of life, in combination with central haemodynamic data.

Patients

Healthy, near-term (>36 weeks of gestation) neonates.

Outcome measures

Pulsatility (PI) and Resistance Indices (RI) patterns and organ-specific conductances, detailed echocardiographic haemodynamic measures.

Results

Twenty-one babies were studied. Doppler morphology and adaptation patterns were distinctly different between the organs (brain, gut and kidney) supporting autonomous vascular regulatory effects. The PI differentiated especially between kidney and other organ flow consistently over time. PI and RI for all three organs decreased. The variance in organ conductance did not explain the variance in 1/PI, indicating that PI is not a measure of resistance. Superior mesenteric artery had the highest velocity with 72 cm/s. Non-invasively acquired pilot serial values in a normal population are given. Patent ductus arteriosus flow remained open at discharge for 36%.

Conclusions

Haemodynamic transitioning patterns assessed by serial Dopplers in healthy near-term neonates differ in brain, gut and kidney: Doppler waveform morphology differs, and PI differentiates renal Doppler morphology, compared with the other organs. While PI and RI decline for all organs, they do not measure resistance. Brain artery velocity increases, mesenteric perfusion is variable and renal Vmax decreases.
Open-label trial of anterior limb of internal capsule–nucleus accumbens deep brain stimulation for obsessive-compulsive disorder: insights gained
Authors: Huys Daniel , Kohl Sina , Baldermann Juan Carlos , Timmermann Lars , Sturm Volker , Visser-Vandewalle Veerle , Kuhn Jens
Published: February 2019

Background

For more than 15 years, deep brain stimulation (DBS) has served as a last-resort treatment for severe treatment-resistant obsessive-compulsive disorder (OCD).

Methods

From 2010 to 2016, 20 patients with OCD (10 men/10 women) were included in a single-centre trial with a naturalistic open-label design over 1 year to evaluate the effects of DBS in the anterior limb of the internal capsule and nucleus accumbens region (ALIC-NAcc) on OCD symptoms, executive functions, and personality traits.

Results

ALIC-NAcc-DBS significantly decreased OCD symptoms (mean Yale-Brown Obsessive Compulsive Scale reduction 33%, 40% full responders) and improves global functioning without loss of efficacy over 1 year. No significant changes were found in depressive or anxiety symptoms. Our study did not show any effect of ALIC-NAcc-DBS on personality traits or executive functions, and no potential outcome predictors were identified in a post hoc analysis. Other than several individual minor adverse events, ALIC-NAcc-DBS has been shown to be safe, but 35% of patients reported a sudden increase in anxiety and anhedonia after acute cessation of stimulation.

Conclusions

We conclude that ALIC-NAcc-DBS is a well-tolerated and promising last-resort treatment option for OCD. The cause of variability in the outcome remains unclear, and the aspect of reversibility must be examined critically. The present data from one of the largest samples of patients with OCD treated with DBS thus far support the results of previous studies with smaller samples.
Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case–control study
Authors: Chu Minjie , Wu Shuangshuang , Wang Wei , Yu Yuhui , Zhang Mingjiong , Sang Lingli , Tian Tian , Lu Yihua , Yuan Weiwei , Huang Qiqing , Yi Min , Gao Yuexia , Xiao Jing , Lian Yulong , Zhuang Xun , Zhang Zuo-Feng , Wu Jianqing
Published: February 2019

Objectives

In a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported.

Methods

We systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case–control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity ofCPMin the promoter. In addition, a two-stage case–control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases.

Results

We found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of theCPMgene was significantly higher in subjects with silicosis compared with healthy controls.

Conclusions

The rs12812500 variant of theCPMgene may increase silicosis susceptibility by affecting the expression ofCPM, which may contribute to silicosis susceptibility with biological plausibility.
Acute postoperative pain is an independent predictor of chronic postsurgical pain following total knee arthroplasty at 6 months: a prospective cohort study
Authors: Buvanendran Asokumar , Della Valle Craig J , Kroin Jeffrey S , Shah Mahendra , Moric Mario , Tuman Kenneth J , McCarthy Robert J
Published: February 2019

Background

Approximately 15% of patients report persistent knee pain despite surgical success following total knee arthroplasty (TKA). The purpose of this study was to determine the association of acute-postsurgical pain (APSP) with chronic postsurgical pain (CPSP) 6 months after TKA controlling for patient, surgical and psychological confounding factors.

Methods

Adult patients with osteoarthritis undergoing primary elective tricompartmental TKA, with the operated knee the primary source of preoperative pain, were studied between March 2011 and February 2017. Patients received standard operative management and a perioperative multimodal analgesia regimen. The primary outcome was CPSP at 6 months. The primary variable of interest was the APSP (weighted mean pain score) for 72 hours postoperatively. Patient, surgical and psychological confounders were assessed using binary logistic regression.

Results

245 cases were analyzed. The incidence of CPSP was 14% (95% CI 10% to 19%). Median APSP values were 4.2 (2.2–5.0) in the CPSP group and 2.8 (1.8–3.7) without CPSP, difference 1.4 (95% CI 0.1 to 1.8, p=0.005). The unadjusted odds for CPSP with an increase of 1 in APSP was 1.46 (95% CI 1.14 to 1.87, p=0.002)). After multivariable risk adjustment, the OR for CPSP for an increase of 1 in the APSP was 1.53 (95% CI 1.12 to 2.09, p=0.008).

Conclusions

APSP is a risk factor for CPSP following TKA even after adjusting for confounding variables such as pain catastrophizing, anxiety, depression and functional status. Studies are needed to determine if APSP is a modifiable risk factor for the development of CPSP.