bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary function testing with tidal breath analyze technique is useful in predicting persistant small airway damage in infants with acute bronchiolitis
Authors: Çelik Elif , Uysal Pınar
Published: July 2020

Background

Due to technical difficulties, lung function in infants is less studied. This prospective cross‐sectional study investigated breathing parameters by using tidal breath analysis (TBA) technique in hospitalized infants with the first‐time acute bronchiolitis (AB).

Methods

This study enrolled 111 infants aged 1 month‐2 years: 61 with AB and 50 healthy controls. Lung function was assessed using TBA technique on the first day of hospitalization and repeated at the 7th and 30th days after the treatment.

Results

The parameters of tPTEF, tPTEF:tE, VT/kg, and tI/tE ratio were still significantly lower at the 30th day of the disease. tPTEF:tE ratio was inversely correlated with hospitalization duration and severity of disease and strongly correlated with VPTEF:VE (r = .876, P < .001) in infants with AB.

Conclusion

Due to restoration of pulmonary function dynamics in the lower respiratory tract was a long‐lasting process, TBA is a useful and easy method for pulmonary function among infants and may help clinicians to predict persistent small airway damage.
Variation in sperm cryosurvival is not modified by replacing the cryoprotectant glycerol with ethylene glycol in bulls
Authors: Gororo Eddington , Makuza Stanley Marshal , Chidzwondo Farisai , Chatiza Fungayi Primrose
Published: July 2020

Contents

Breed and sire differences in sperm cryosurvival have been noted, with negative implications for sperm cryobanking and assisted reproduction programmes. This study hypothesized that these differences could be modified by using lower molecular weight cryoprotectants. Therefore, the effect of replacing glycerol (GLY) with ethylene glycol (EG) on differential cryosurvival of semen from two Sanga cattle breeds (Mashona vs. Tuli) was determined. Three to five ejaculates were collected from each of ten bulls (3‐8 years) by electro‐ejaculation, diluted in three Tris‐egg yolk extenders (Triladyl®, 7% GLY‐based and 7% EG‐based) and evaluated for sperm motility, viability and morphology at three time periods (fresh – 0 hr, pre‐freeze – 4 hr and post‐thaw). Tuli bulls produced larger (11.8 ± 0.31 ml vs. 8.5 ± 0.38 ml) and more concentrated ejaculates of lower fresh semen quality. Breeds differed across time for motility and morphology, but not viability. Mashona bull semen had significantly higher motility and normal morphology values at each sampling time. Bulls classified as poor freezers had lower concentration (0.70 ± 0.09 × 109 sperm/ml vs. 1.37 ± 0.10 × 109 sperm/ml), sperm motility index (SMI, 35.0 ± 3.4 % vs. 67.8 ± 2.1 %) and viability (69.7 ± 1.1 % vs. 75.7 ± 1.0 %) compared to good freezers. Maintenance of semen quality by GLY and EG did not differ between breeds, poor and good freezers, or age groups. The interaction breed by extender across time did not reach statistical significance for all variables. The study revealed that bull and breed variation in sperm quality and cryosurvival is not modified by replacing GLY with EG, suggesting that cryostress tolerance of sperm may be under control of mechanisms other than differential response to GLY cytotoxicity.
Systemic sclerosis: Update for oral health care providers
Authors: Alhendi Fatmah J. , Werth Victoria P. , Sollecito Thomas P. , Stoopler Eric T.
Published: July 2020

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disease of unknown origin characterized by an uncontrolled inflammatory process resulting in fibrosis of the skin, internal organs and vasculopathy. Manifestations of SSc are heterogenous and can include pulmonary, cardiac, neural, renal, muscular, cutaneous and orofacial complications. Recent scientific advances have led to a better understanding of disease etiopathogenesis and the development of a new classification system. Therapeutic management is often multidisciplinary and targeted toward the affected organs. Oral health care providers (OHCPs) should be familiar with SSc, particularly as it relates to its impact on the orofacial region and modifications to delivery of oral health care for patients with this condition.
Revenge as social interaction: Merging social psychological and interpersonal communication approaches to the study of vengeful behavior
Authors: Boon Susan D. , Yoshimura Stephen M.
Published: July 2020

The purpose of this essay is to review and assess the benefits of merging social psychological and communication theory‐based approaches to the study of vengeful behavior in interpersonal interactions. We first outline the parallel but complementary perspectives that each discipline takes to the conceptualization of revenge. From there, we identify some of the core features that would be present in an integrated approach that conceptualizes revenge as an interpersonal process (i.e., an interaction or exchange), and then highlight new directions for both inquiry and theory building that an integrative approach reveals as worthy of scholarly pursuit. We argue that conceptualizing and studying revenge in ways that blend both social psychological and communication‐based views offers numerous opportunities to examine the dynamics between a provoking party and an avenger, and provides a richer and more insightful theoretical understanding of vengeful behavior than either perspective could offer alone.
Utterances, Sub‐utterances and Token‐Reflexivity
Authors: Ciecierski Tadeusz
Published: July 2020

The popular interpretation of token‐reflexivism states that at the level of logical form, indexicals and demonstratives are disguised descriptions that employ complex demonstratives or special quotation‐mark names involving particular tokens of the appropriate expression‐types. In this article I first demonstrate that this interpretation of token‐reflexivism is only one of many, and that it is better to think of token‐reflexivism as denoting a family of distinct theoretical frameworks. Second, I contrast two interpretations of the idea of the token‐reflexive paraphrase of an indexical sentence. The utterance approach claims that token‐reflexive paraphrases involve tokens of entire utterances. The sub‐utterance approach maintains that token‐reflexive paraphrases involve tokens of the particular indexical words used in the utterance. Next, I pose a problem that shows that neither of the two approaches is correct. The problem shows that the only viable version of the token‐reflexive proposition must somehow take into account the referential intentions of the speaker of the context. Therefore I conclude the article by sketching the framework of restricted intentional token‐reflexivism. I argue that it is an attractive semantic theory of distributed utterances that, among other things, enables automatic and intentional indexicals to be distinguished.
Seasonality and coinfection of bronchiolitis: epidemiological specificity and consequences in terms of prophylaxis in tropical climate
Authors: Najioullah Fatiha , Bancons Pierre , Césaire Raymond , Fléchelles Olivier
Published: July 2020

Objective

To describe the viruses involved, seasonality and coinfection in hospitalised children with suspected bronchiolitis.

Methods

Over the period 1/07/2007 to 31/12/2008, all children hospitalised for bronchiolitis in the paediatric ward were prospectively included, and had respiratory syncytial virus (RSV) screenings. We retrospectively tested all samples for RSVA, RSVB, rhinovirus (RV), human metapneumovirus, parainfluenza 1, 2, 3, 4, influenza A and influenza B.

Results

198 children were tested, and 23% were negative for all viruses. RSVA was predominant in 2008 (64% of all viruses) and RSVB in 2007 (66% of all viruses). RV was frequent during both seasons (24% of all viruses). Flu was not found during the study period. Virus distribution was similar regardless of season or age, and identical to typical patterns in temperate countries. Coinfections were less frequent than in temperate regions because respiratory virus seasons seem to be better separated. The bronchiolitis season started in August and finished in December with a peak in October.

Conclusion

The specific seasonality of bronchiolitis infection requires palivizumab prophylaxis starting in early July for high‐risk infants.
Comparison of chlorination and chloramination practices on microbial inactivation efficiencies within a scaled‐up water distribution network using central composite design
Authors: Khan Romana , Hashmi Imran , Qureshi Amrah , Rasheed Sajida
Published: July 2020

Disinfection practices reduce the incidence of water‐borne diseases but may result in formation of disinfection byproducts (DBPs) in raw water that are reported to be carcinogenic. Central composite design (CCD) was employed in the present study for optimization of disinfectant dose and contact time with the rationale to evaluate if an optimal balance could be achieved between minimal DBPs formation and effective microbial inactivation with either free or combined chlorine in treated water within a lab‐scale prototype network to simulate real water distribution network conditions. After a series of experimental runs based upon design of experiments (DoE) by CCD, dose was found to be the most significant factor (P < 0.01) in determining DBPs formation in both disinfectant’s applications. Where, contact time significantly (P < 0.01) affected bacterial inactivation in chlorination experiments, in contrast, dose was effective in chloramination experiments. Thus, it was concluded that the optimal balance may be achieved in the water networks with the help of multifactorial optimization when disinfectant dose was maintained near 3 mg/L as applied chlorine dose in both disinfection cases, while contact time was 62 and 155 min for chlorine and chloramine, respectively.
A study of external mass transfer effect on biodegradation of phenol using low‐density polyethylene immobilized Bacillus flexus GS1 IIT (BHU) in a packed bed bioreactor
Authors: Swain Ganesh , Sonwani Ravi Kumar , Giri Balendu Shekhar , Singh Ram Sharan , Jaiswal Ravi Prakash , Rai Birendra Nath
Published: July 2020

The impact of external mass transport on the biodegradation rate of phenol in a packed bed bioreactor (PBBR) was studied. A potential bacterial species, Bacillus flexus GS1 IIT (BHU), was isolated from the petroleum‐contaminated soil. Low‐density polyethylene (LDPE) immobilized with the B. flexus GS1 IIT (BHU) was used as packing material in the PBBR. The PBBR was operated by varying the inlet feed flow rate from 4 to 10 mL/min, and the corresponding degradation rate coefficients were found to be in the range of 0.119–0.157 L/g h. In addition, the highest removal rate of phenol was obtained to be 1.305 mg/g h at an inlet feed rate of 10 mL/min. The external mass transfer was studied using the model . A new empirical correlation for the biodegradation of phenol in the PBBR was developed after the evaluation at various values of K and n.
The test function conjecture for local models of Weil-restricted groups
Authors: Haines Thomas J. , Richarz Timo
Published: July 2020

We prove the test function conjecture of Kottwitz and the first named author for local models of Shimura varieties with parahoric level structure attached to Weil-restricted groups, as defined by B. Levin. Our result covers the (modified) local models attached toallconnected reductive groups over$p$-adic local fields with$p\geqslant 5$. In addition, we give a self-contained study of relative affine Grassmannians and loop groups formed using general relative effective Cartier divisors in a relative curve over an arbitrary Noetherian affine scheme.
Heat acclimation during low‐intensity exercise increases and Hsp72, but not markers of mitochondrial biogenesis and oxidative phosphorylation, in skeletal tissue
Authors: Mang Zachary A. , Fennel Zachary J. , Realzola Rogelio A. , Wells Andrew D. , McKenna Zachary , Droemer Christian , Houck Jonathan M. , Nava Roberto C. , Mermier Christine M. , Amorim Fabiano T.
Published: July 2020

New Findings

What is the central question of this study?

Heat acclimation increases tolerance to exercise performed in the heat and may improve maximal oxygen uptake (VO2max) and performance in temperate environments. However, it is unknown if HA affects the expression of proteins related to mitochondrial biogenesis and oxidative capacity in skeletal muscle.

What is the main finding and its importance?

We showed that heat acclimation increased VO2max in a temperate environment but did not change markers of mitochondrial biogenesis and oxidative phosphorylation in the skeletal muscle.

Heat acclimation (HA) increases tolerance to exercise performed in the heat and may improve maximal oxygen uptake () in temperate environments. However, it is unknown if HA affects the expression of proteins related to mitochondrial biogenesis and oxidative capacity in skeletal muscle. The purpose of this study was to investigate the effect of HA on skeletal muscle markers of mitochondrial biogenesis and oxidative phosphorylation in recreationally trained adults. Thirteen (7 males and 6 females) individuals underwent 10 days of HA. Participants performed two 45 min bouts of exercise (walking at 30–40% maximal velocity at 3% grade) with 10 min rest per session in a hot environment (∼42°C and 30–50% relative humidity). , ventilatory thresholds (VT), and protein expression of peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α), mitochondrial transcription factor A (TFAM), calcium/calmodulin‐dependent protein kinase (CaMK), electron transport chain (ETC) complexes I–IV, and heat shock protein 72 (Hsp72) in skeletal muscle were measured pre‐ and post‐HA. Comparing day 1 to day 10, HA was confirmed by lower resting core temperature (Tcore) (P = 0.026), final Tcore (P < 0.0001), mean heart rate (HR) (P = 0.002), final HR (P = 0.003), mean ratings of perceived exertion (RPE) (P = 0.026) and final RPE (P = 0.028). Pre‐ to post‐HA (P = 0.045) increased but VT1 (P = 0.263) and VT2 (P = 0.239) were unchanged. Hsp72 (P = 0.007) increased, but skeletal muscle protein expression (PGC‐1α, P = 0.119; TFAM, P = 0.763; CaMK, P = 0.19; ETC I, P = 0.629; ETC II, P = 0.724; ETC III, P = 0.206; ETC IV, P = 0.496) were not affected with HA. HA during low‐intensity exercise increased in a temperate environment and Hsp72 but it did not affect markers of mitochondrial biogenesis and oxidative phosphorylation in the skeletal muscle.
Combination of curcumin with autologous transplantation of adult neural stem/progenitor cells leads to more efficient repair of damaged cerebral tissue of rat
Authors: Attari Fatemeh , Ghadiri Tahereh , Hashemi Mansoureh
Published: July 2020

New Findings

What is the central question of this study?

Can the neuroprotective agent curcumin affect restorative action of neural stem/progenitor cells in the injured rat brain?

What is the main finding and its importance?

In the presence of curcumin, transplantation of neural stem/progenitor cells in the context of PuraMatrix reduced lesion size and reactive inflammatory responses, and boosted survival rate of grafted neurons. In addition it improved the neurological status of injured animals. This could be beneficial in designing new therapeutic approaches for brain injury based on this combination therapy.

Traumatic brain injury (TBI) is catastrophic neurological damage associated with substantial morbidity and mortality. To date, there is no specific treatment for restoring lost brain tissue. In light of the complex pathology of brain injury, the present study evaluated the effects of combination therapy using autologous neural stem/progenitor cells (NS/PCs), PuraMatrix (PM) and curcumin in an animal model of brain injury. After stereotactic biopsy of subventricular zone tissue and culture of NS/PCs, 36 male Wistar rats (150–200 g) were randomly divided into six groups receiving dimethyl sulfoxide (DMSO),  curcumin (100 mg kg−1 in DMSO), PM + curcumin (100 mg kg−1 in DMSO), NS/PCs + curcumin (100 mg kg−1 in DMSO), NS/PCs + PM + curcumin (100 mg kg−1 in DMSO) and NS/PCs + PM + curcumin (1 µm) following acute brain injury. The animals were evaluated in term of neurological status for 4 weeks, then decapitated. Nissl and TUNEL staining and immunohistochemistry for bromodeoxyuridine, glial fibrillary acidic protein, doublecortin, Map2, Olig2, Iba1 and CD68 were performed. We found that combination therapy by NS/PCs + PM + curcumin reduced the lesion size, astrogliosis, macrophage and microglial reaction as well as the number of apoptotic cells. Moreover, the transplanted cells were able to survive and differentiate after 4 weeks. Besides these findings, transplantation of NS/PCs in the context of PM and curcumin improved the neurological status of injured animals. In conclusion, our data suggest that this combination therapy can be beneficial in developing future therapeutic approaches for brain injury.
Modulation of information processing by AMPA receptor auxiliary subunits
Authors: Jacobi Eric , von Engelhardt Jakob
Published: July 2020

AMPA‐type glutamate receptors (AMPARs) are key molecules of neuronal communication in our brain. The discovery of AMPAR auxiliary subunits, such as proteins of the TARP, CKAMP and CNIH families, fundamentally changed our understanding of how AMPAR function is regulated. Auxiliary subunits control almost all aspects of AMPAR function in the brain. They influence AMPAR assembly, composition, structure, trafficking, subcellular localization and gating. This influence has important implications for synapse function. In the present review, we first discuss how auxiliary subunits affect the strength of synapses by modulating number and localization of AMPARs in synapses as well as their glutamate affinity, conductance and peak open probability. Next we explain how the presence of auxiliary subunits alters temporal precision and integrative properties of synapses by influencing gating kinetics of the receptors. Auxiliary subunits of the TARP and CKAMP family modulate synaptic short‐term plasticity by increasing anchoring of AMPARs in synapses and by altering their desensitization kinetics. We then describe how auxiliary subunits of the TARP, CKAMP and CNIH families are involved in Hebbian and homeostatic plasticity, which can be explained by their influence on surface trafficking and synaptic targeting. In conclusion, the series of studies covered in this review show that auxiliary subunits play a pivotal role in controlling information processing in the brain by modulating synaptic computation.

image
Paracellular bicarbonate flux across human cystic fibrosis airway epithelia tempers changes in airway surface liquid pH
Authors: Thornell Ian M. , Rehman Tayyab , Pezzulo Alejandro A. , Welsh Michael J.
Published: July 2020

Key points

Cl− and HCO3− had similar paracellular permeabilities in human airway epithelia.

PCl/PNa of airway epithelia was unaltered by pH 7.4 vs. pH 6.0 solutions.

Under basal conditions, calculated paracellular HCO3− flux was secretory.

Cytokines that increased airway surface liquid pH decreased or reversed paracellular HCO3− flux.

HCO3− flux through the paracellular pathway may counterbalance effects of cellular H+ and HCO3− secretion.

Airway epithelia control the pH of airway surface liquid (ASL), thereby optimizing respiratory defences. Active H+ and HCO3− secretion by airway epithelial cells produce an ASL that is acidic compared with the interstitial space. The paracellular pathway could provide a route for passive HCO3− flux that also modifies ASL pH. However, there is limited information about paracellular HCO3− flux, and it remains uncertain whether an acidic pH produced by loss of cystic fibrosis transmembrane conductance regulator anion channels or proinflammatory cytokines might alter the paracellular pathway function. To investigate paracellular HCO3− transport, we studied differentiated primary cultures of human cystic fibrosis (CF) and non‐CF airway epithelia. The paracellular pathway was pH‐insensitive at pH 6.0 vs. pH 7.4 and was equally permeable to Cl− and HCO3−. Under basal conditions at pH ∼6.6, calculated paracellular HCO3− flux was weakly secretory. Treating epithelia with IL‐17 plus TNFα alkalinized ASL pH to ∼7.0, increased paracellular HCO3− permeability, and paracellular HCO3− flux was negligible. Applying IL‐13 increased ASL pH to ∼7.4 without altering paracellular HCO3− permeability, and calculated paracellular HCO3− flux was absorptive. These results suggest that HCO3− flux through the paracellular pathway counterbalances, in part, changes in the ASL pH produced via cellular mechanisms. As the pH of ASL increases towards that of basolateral liquid, paracellular HCO3− flux becomes absorptive, tempering the alkaline pH generated by transcellular HCO3− secretion.
Stable Grasp Control With a Robotic Exoskeleton Glove
Authors: Vanteddu Teja , Ben-Tzvi Pinhas
Published: July 2020

An exoskeleton robotic glove intended for patients who have suffered paralysis of the hand due to stroke or other factors has been developed and integrated. The robotic glove has the potential to aid patients with grasping objects as part of their daily life activities. Grasp stability was studied and researched by various research groups, but mainly focused on robotic grippers by devising conditions for a stable grasp of objects. Maintaining grasp stability is important so as to reduce the chances of the object slipping and dropping. But there was little focus on the grasp stability of robotic exoskeleton gloves, and most of the research was focused on mechanical design. A robotic exoskeleton glove was developed as well as novel methods to improve the grasp stability. The glove is constructed with rigidly coupled four-bar linkages attached to the finger tips. Each linkage mechanism has one-DOF (degree of freedom) and is actuated by a linear series elastic actuator (SEA). Two methods were developed to satisfy two of the conditions required for a stable grasp. These include deformation prevention of soft objects, and maintaining force and moment equilibrium of the objects being grasped. Simulations were performed to validate the performance of the proposed algorithms. A battery of experiments was performed on the integrated prototype in order to validate the performance of the algorithms developed.
Design of an Accurate and Stiff Wooden Industrial Robot: First Steps Toward Robot Eco-sustainable Mechanical Design
Authors: Briot Sébastien , Kaci Lila , Boudaud Clément , Llevat Pamiès David , Lafoux Pauline , Martinet Philippe
Published: July 2020

This article investigates the feasibility of replacing metal robot links by wooden bodies for eco-sustainable design’s purpose. Wood is a material with low environmental impact and a good mass-to-stiffness ratio. However, it has significant dimensional and mechanical variabilities. This is an issue for industrial robots that must be accurate and stiff. To guarantee stiffness and accuracy performance of a wooden robot, we propose an integrated design process combining (i) proper wood selection, (ii) adequate sensor-based control strategies to ensure robot accuracy, and (iii) a robust design approach dealing with wood uncertainties. Based on the use of this integrated design process, a prototype of a wooden five-bar mechanism is designed and manufactured. Experimental results show that it is realistic to design a wooden robot with performance compatible with industry requirements in terms of stiffness (deformations lower than 400 μm for 20 N loads) and accuracy (repeatability lower than 60 μm), guaranteed in a workspace of 800 mm × 200 mm. This study provides a first step toward the eco-sustainable mechanical design of robots.
Opportunities and Challenges in Metal Forming for Lightweighting: Review and Future Work
Authors: Cao Jian , Banu Mihaela
Published: July 2020

The purposes of this review are to summarize the historical progress in the last 60 years of lightweight metal forming, to analyze the state-of-the-art, and to identify future directions in the context of Cyber-physically enabled circular economy. In honoring the 100th anniversary of the establishment of the Manufacturing Engineering Division of ASME, this review paper first provides the impact of the metal forming sector on the economy and historical perspectives of metal forming research work published by the ASME Journal of Manufacturing Science and Engineering, followed by the motivations and trends in lightweighting. To achieve lightweighting, one needs to systematically consider: (1) materials and material characterization; (2) innovative forming processes; and (3) simulation tools for integrated part design and process design. A new approach for process innovation, i.e., the Performance-Constraints-Mechanism-Innovation (PCMI) framework, is proposed to systematically seek new processes. Finally, trends and challenges for the further development in circular economy are presented for future exploration.
The Molecular Complex between Staphylococcal Adhesin SpsD and Fibronectin Sustains Mechanical Forces in the Nanonewton Range
Authors: Viela Felipe , Mathelié-Guinlet Marion , Pietrocola Giampiero , Speziale Pietro , Dufrêne Yves F.
Published: July 2020

Binding of
Staphylococcus pseudintermedius
surface proteins SpsD and SpsL to fibronectin (Fn) plays a critical role in the invasion of canine epithelial cells. Here, we discover that both adhesins have different mechanisms for binding to Fn. The force required to separate SpsD from Fn is extremely strong, consistent with the unusual β-sheet organization of a high-affinity tandem β-zipper. By contrast, unbinding of the SpsL-Fn complex involves the sequential rupture of single weak bonds. Our findings may be of biological relevance as SpsD and SpsL are likely to play complementary roles during invasion. While the SpsD β-zipper supports strong bacterial adhesion and triggers invasion, the weak SpsL interaction would favor fast detachment, enabling the pathogen to colonize new sites.
Inhibition of Fatty Acid Oxidation Promotes Macrophage Control of Mycobacterium tuberculosis
Authors: Chandra Pallavi , He Li , Zimmerman Matthew , Yang Guozhe , Köster Stefan , Ouimet Mireille , Wang Han , Moore Kathyrn J. , Dartois Véronique , Schilling Joel D. , Philips Jennifer A.
Published: July 2020

Mycobacterium tuberculosis
(Mtb) is the leading infectious disease killer worldwide. We discovered that intracellular Mtb fails to grow in macrophages in which fatty acid β-oxidation (FAO) is blocked. Macrophages treated with FAO inhibitors rapidly generate a burst of mitochondria-derived reactive oxygen species, which promotes NADPH oxidase recruitment and autophagy to limit the growth of Mtb. Furthermore, we demonstrate the ability of trimetazidine to reduce pathogen burden in mice infected with Mtb. These studies will add to the knowledge of how host metabolism modulates Mtb infection outcomes.
Genomic Analysis of Bovine Staphylococcus aureus Isolates from Milk To Elucidate Diversity and Determine the Distributions of Antimicrobial and Virulence Genes and Their Association with Mastitis
Authors: Naushad Sohail , Nobrega Diego B. , Naqvi S. Ali , Barkema Herman W. , De Buck Jeroen
Published: July 2020

Staphylococcus aureusis a major cause of bovine intramammary infections, leading to significant economic losses to dairy industry in Canada and worldwide. There is a lack of knowledge regarding genetic diversity, the presence of antimicrobial resistance (AMR), and virulence genes forS. aureusisolated from bovine milk in Canada. Based on whole-genome sequencing and genomic analysis, we have determined the phylogeny and diversity ofS. aureusin bovine milk and concluded that it had a large accessory genome, limited distribution of AMR genes, variable VF gene profiles and sequence types (ST), and clonal complex (CC)-specific pathogenic potentials. Comprehensive information on the population structure, as well as the virulence and resistance characteristics ofS. aureusfrom bovine milk, will allow for source attribution, risk assessment, and improved therapeutic approaches in cattle.
Host and Parasite Transcriptomic Changes upon Successive Plasmodium falciparum Infections in Early Childhood
Authors: Bradwell Katie R. , Coulibaly Drissa , Koné Abdoulaye K. , Laurens Matthew B. , Dembélé Ahmadou , Tolo Youssouf , Traoré Karim , Niangaly Amadou , Berry Andrea A. , Kouriba Bourema , Plowe Christopher V. , Doumbo Ogobara K. , Lyke Kirsten E. , Takala-Harrison Shannon , Thera Mahamadou A. , Travassos Mark A. , Serre David
Published: July 2020

We show that dual RNA-seq from patient blood samples allows characterization of host/parasite interactions during malaria infections and can provide a solid framework to study the acquisition of antimalarial immunity, as well as the adaptations of
P. falciparum
to malaria-experienced hosts.
Thermotectonic evolution of the Paleozoic granites along the Shangdan suture zone (central China): Crustal growth and differentiation by magma underplating in an orogenic belt
Authors: Qin Jiang-Feng , Lai Shao-Cong , Long Xiao-Ping , Zhang Ze-Zhong , Ju Yin-Juan , Zhu Ren-Zhi , Wang Xing-Ying , Li Yong-Fei , Wang Jiang-Bo , Li Tong
Published: July 2020

The nature of source rocks and the pressure-temperature-hydration (P-T-H2O) condition are the two main factors that control the geochemical properties of granites. Therefore, the evolution of P-T-H2O conditions can be used to deduce the tectonic setting of granites. In this paper, we report on three Paleozoic granite plutons along the Shangdan suture that revealed increasing melting temperature and decreasing pressure from 437 to 403 Ma, suggesting a crustal thinning process. The Tieyupu granodiorites (437 ± 4 Ma) display Na-rich adakite affinity, i.e., SiO2 = 69.1–70.1 wt%, Na2O/K2O = 1.9–2.26, positive zircon εHf(t) values (+4.29 to +12.04), and high Sr/Y (137–160) and Y/Yb (9.89–10.25) ratios, implying a garnet-rich residue in their source. In combination with moderate zircon saturation temperatures (814–822 °C), we infer that the Tieyupu granodiorites were formed by melting of Neoproterozoic metabasites under high-pressure (>1.5 GPa) and moderate-temperature (HP-MT) conditions. The Liangchahe granodiorites (415 ± 8 Ma) also display Na-rich adakite affinity, i.e., higher Na2O/K2O (2.16–3.11) and lower Sr/Y (77–88) ratios, and higher zircon saturation temperatures (854–874 °C), and they are interpreted to have been derived from melting of metabasites under moderate-pressure (>1.0 GPa) and high-temperature (MP-HT) conditions. Their variable zircon εHf(t) values (−14.97 to +9.80) and the existence of zircon xenocrysts suggest that the primitive adakitic melts were assimilated by evolved crustal components. The Yaogou monzogranites (403 ± 4 Ma) have the highest K2O/Na2O (0.81–1.00) ratios and total rare earth element (ΣREE; 105–191 ppm) contents, lowest Sr/Y (14–43) ratios, positive zircon εHf(t) values (+6.79 to +12.22), and highest zircon saturation temperatures (891–973 °C), showing they were formed by high-temperature melting of intermediate rocks under low-pressure conditions (<1.0 GPa). The evolution of P-T conditions revealed by these three granites suggests that crustal growth and differentiation were related to gradual extensional and melting of mafic protoliths in the orogenic belt.
Successful treatment of resistant HCV in a patient with Child-Pugh B cirrhosis using sofosbuvir and glecaprevir/pibrentasvir
Authors: Islam Munim , Nicholas Sarah , Oakley Rhys , Healy Brendan
Published: July 2020

Treatments for hepatitis C are now well tolerated with very high rates of sustained virological response and almost all patients have a suitable and effective treatment option. However, treatment options remain limited for a minority of patients and are limited for patients with Child-Pugh B or C cirrhosis due to the risk of decompensation with protease inhibitors. We present a case of successful treatment with glecaprevir/pibrentasvir (Maviret) and sofosbuvir in a patient with Child-Pugh B cirrhosis and resistant virus who had failed three previous attempts of treatment including two courses of direct acting antiviral agents and in whom liver transplantation was deemed unsuitable. We propose that the balance of risks favours a trial of treatment with protease inhibitors in some circumstances in patients with Child-Pugh B cirrhosis where no other suitable alternatives including treatment post liver transplantation are available/appropriate.
Treatment strategies for asymptomatic carotid artery stenosis in the era of lipid-lowering drugs: protocol for a systematic review and network meta-analysis
Authors: Bai Xuesong , Feng Yao , Li Long , Yang Kun , Wang Tao , Luo Jichang , Wang Xue , Ling Feng , Ma Yan , Jiao Liqun
Published: July 2020

Introduction

Carotid endarterectomy (CEA), carotid artery stenting (CAS) and best medical therapy (BMT) are the major treatments used for significant asymptomatic carotid artery stenosis (ACAS, ≥50%). However, the widespread use of lipid-lowering drugs in this century has improved BMT outcomes. This study aims to compare the treatment efficacy of current BMT, CEA+BMT and CAS+BMT in patients with significant ACAS.

Methods and analysis

This protocol was designed based on the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Publication time for studies will be set from 1 January 2000 to 1 June 2020. We will search three databases: PubMed, EMBASE and The Cochrane Library. Suitable randomised controlled studies will be screened. The primary outcomes will include short-term and long-term mortality, stroke and myocardial infarction. OR and HR for dichotomous data and time-to-event data with 95% CIs will be calculated. Treatment effects among different therapies will be ranked according to the surface under the cumulative ranking curve and mean rank. A comprehensive evaluation of the risk of bias, heterogeneity and transitivity will be performed before data synthesis. Consistency and evidence quality will also be assessed.

Ethics and dissemination

There will be no need for ethics approval as this systematic review is a summary and analysis of existing literature. Final results may be presented in international conferences or a peer-reviewed journal.

PROSPERO registration number

CRD42019138942.
Heparin-binding protein as a biomarker of gastrointestinal dysfunction in critically ill patients: a retrospective cross-sectional study in China
Authors: Sun Jia-Kui , Shen Xiao , Sun Xin-Pei , Wang Xiang , Zhang Wen-Hao , Shi Qian-Kun , Mu Xin-Wei
Published: July 2020

Objective

To investigate the association of plasma heparin-binding protein (HBP) with the development of acute gastrointestinal injury (AGI) in critically ill patients.

Design

Clinical retrospective cross-sectional study.

Setting

A general teaching hospital in China.

Participants

Adult patients (age ≥18 years) admitted to our department with an intensive care unit (ICU) stay ≥5 days.

Main outcome measures

HBP levels were recorded twice or more within 5 days after admission. The initial AGI grades and the worst AGI grades within 5 days after admission, the number of patients receiving total enteral nutrition (TEN) and the number of patients with feeding intolerance (FI) and with sepsis were also recorded, along with some clinical severity and outcome variables.

Results

From June 2018 to May 2019, 221 patients were enrolled in this study. We divided patients into four groups based on the HBP values: HBP ≤20 ng/mL, 20<HBP ≤50 ng/mL, 50100 ng/mL. Significant differences were found in the ratios of AGI deterioration and TEN and the incidence rates of FI and sepsis among the four groups. Differences were also found among the groups regarding the worst AGI grades. The area under receiver operating characteristic curves for AGI deterioration, severe AGI (grades II or above), TEN and FI were 0.738 (p=0.001), 0.774 (p<0.001), 0.810 (p<0.001) and 0.729 (p=0.001), respectively. The optimal HBP cut-off values for AGI deterioration and severe AGI were 53.27 ng/mL and 41.26 ng/mL, respectively. However, no differences in ICU duration or 28-day mortality were found.

Conclusions

HBP levels were associated with gastrointestinal dysfunction in critically ill patients. Increased HBP was positively correlated with sepsis but it was not correlated with 28-day mortality.
Exploring the multiple policy objectives for primary care networks: a qualitative interview study with national policy stakeholders
Authors: Checkland Kath , Hammond Jonathan , Warwick-Giles Lynsey , Bailey Simon
Published: July 2020

Objectives

English general practice is suffering a workforce crisis, with general practitioners retiring early and trainees reluctant to enter the profession. To address this, additional funding has been offered, but only through participation in collaborations known as primary care networks (PCNs). This study explored national policy objectives underpinning PCNs and the mechanisms expected to help achieve these, from the perspective of those driving the policy.

Design

Qualitative semistructured interviews and policy document analysis.

Setting and participants

National-level policy maker and stakeholder interviewees (n=16). Policy document analysis of the Network Contract Direct Enhanced Service draft service specifications.

Analysis

Interviews were transcribed, coded and organised thematically according to policy objectives and mechanisms. Thematic data were organised into a matrix so prominent elements can be identified and emphasised accordingly. Themes were considered alongside objectives embedded in PCN draft service delivery requirements.

Results

Three themes of policy objectives and associated mechanisms were identified: (1) supporting general practice, (2) place-based interorganisational collaboration and (3) primary care ‘voice’. Interviewees emphasised and sequenced themes differently, suggesting meeting objectives for one was necessary to realise another. Interviewees most closely linked to primary care emphasised the importance of theme 1. The objectives embedded in draft service delivery requirements primarily emphasised theme 2.

Conclusions

These policy objectives are not mutually exclusive but may imply different approaches to prioritising investment or necessitate more explicit temporal sequencing, with the stabilisation of a struggling primary care sector probably needing to occur before meaningful engagement with other community service providers can be achieved or a ‘collective voice’ is agreed. Multiple objectives create space for stakeholders to feel dissatisfied when implementation details do not match expectations, as the negative reaction to draft service delivery requirements illustrates. Our study offers policy makers suggestions about how confidence in the policy might be restored by crafting delivery requirements so all groups see opportunities to meet favoured objectives.
Time to diagnosis of idiopathic pulmonary fibrosis in the IPF-PRO Registry
Authors: Snyder Laurie D , Mosher Christopher , Holtze Colin H , Lancaster Lisa H , Flaherty Kevin R , Noth Imre , Neely Megan L , Hellkamp Anne S , Bender Shaun , Conoscenti Craig S , de Andrade Joao A , Whelan Timothy PM
Published: July 2020

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality. Patient characteristics associated with diagnostic delays are not well described.

Methods

Subjects who had not been diagnosed with IPF prior to referral and received a new diagnosis of IPF at an enrolling centre for the IPF-PRO (IdiopathicPulmonaryFibrosisProspective Outcomes) Registry were characterised as having a longer (>1 year) or shorter (≤1 year) time from symptom onset to diagnosis and from first imaging evidence of fibrosis to diagnosis. Patient characteristics, evaluations and time to death or lung transplant were compared between these cohorts.

Results

Among 347 patients with a symptom onset date, 49% were diagnosed with IPF >1 year after symptom onset. These patients were slightly younger and had more cardiac comorbidities than patients diagnosed ≤1 year after symptom onset. Among 454 patients with a date for imaging evidence of fibrosis, 78% were diagnosed with IPF ≤1 year later. A greater proportion of patients with >1 year versus ≤1 year from imaging evidence of fibrosis to diagnosis had cardiac comorbidities and gastro-oesophageal reflux. There was no significant difference in time to death or lung transplant between groups by time to diagnosis.

Conclusions

The time from symptom onset to diagnosis remains over 1 year in approximately half of the patients with IPF, but once imaging evidence is obtained, most of the patients are diagnosed within a year. Cardiac conditions and gastro-oesophageal disorders were more commonly reported in patients with a longer time to diagnosis.
Meaning in life and quality of life: palliative care patients versus the general population
Authors: Bernard Mathieu , Berchtold André , Strasser Florian , Gamondi Claudia , Borasio Gian Domenico
Published: July 2020

Background and objectives

Meaning in life (MIL) represent a key topic in palliative care. The aims of this study were to explore (1) the differences in perceived MIL and in the meaning-relevant life areas between a representative sample of the Swiss population and palliative care patients, and (2) to what extent MIL can be considered as a significant predictor of quality of life (QOL).

Methods

A cross-sectional study was conducted separately for the patients (face-to-face interviews) and the general population (telephone survey). MIL was measured with the Schedule for Meaning in Life Evaluation (SMILE) and QOL with a single-item visual analogue scale (0–10). Sociodemographic variables were controlled for in the analyses.

Results

206 patients and 1015 participants from the Swiss population completed the protocol. Results indicated high MIL scores in both populations even if the difference was significant (patients 81.9 vs general population 87, p<0.001). Patients were more likely to cite ‘family’ (OR=1.78), ‘social relations’ (OR=1.9), ‘spirituality and religion’ (OR=3.93), ‘social commitment’ (OR=1.94) and ‘growth’ (OR=2.07), and less likely to cite ‘finances’ (OR=0.15) and ‘health’ (OR=0.21) as MIL-relevant areas. The SMILE scores and MIL areas explained 21.8% of the QOL variance for the patients and 15.1% for the representative sample.

Conclusions

Our data emphasise the importance of MIL as a contributor to QOL in both populations. It highlights the importance of the life areas contributing to MIL, especially social interactions for both populations, and spirituality and areas related to growth in palliative care patients.
Prone positioning in patients treated with non-invasive ventilation for COVID-19 pneumonia in an Italian emergency department
Authors: Bastoni Davide , Poggiali Erika , Vercelli Andrea , Demichele Elena , Tinelli Valentina , Iannicelli Teresa , Magnacavallo Andrea
Published: July 2020

We report the experience of prone ventilation in selected patients treated with helmet non-invasive ventilation (NIV) continuous positive airway pressure (CPAP) for acute respiratory failure in COVID-19 pneumonia. Preliminary results showed an improvement in the PaO2value and PaO2/FiO2ratio after 1 hour of prone ventilation. No variation of the lung ultrasound pattern before and after prone ventilation has been detected. At the time of writing, we attempted proning with helmet NIV CPAP in 10 patients. In 4 out of 10 patients, the attempt failed due to lack of compliance of the patient, scarce pain control even with ongoing treatment and refusal by the patient to prone positioning.
Alcohol consumption and internalising disorders in young adults of ALSPAC: a population-based study
Authors: Fernandes Gwen Sascha , Lewis Gemma , Hammerton Gemma , Abeysekera Kushala , Mahedy Liam , Edwards Alexis , Lewis Glyn , Hickman Matthew , Heron Jonathan
Published: July 2020

Introduction

Depression and harmful alcohol consumption contribute significantly to the global health burden, but in young adults, this relationship is under-researched and conflicted. The aim of this study was to determine the sex-based prevalence and the association between internalising disorders such as depression and alcohol use disorders.

Method

Using the Avon Longitudinal Study of Parents and Children, we assessed the sex-specific prevalence of International Classification of Diseases,Tenth Revision diagnosed generalised anxiety disorder (GAD), depression and fear-based anxieties (FBA) at 24 years (n=3572). We examined the association between internalising disorders and alcohol consumption using the Alcohol Use Disorder Identification Test for Consumption 5+ threshold and Diagnostic and Statistical Manual on Mental Disorders defined criteria for alcohol dependence.

Results

Women reported more GAD (11.6% vs 6.5%), depression (13.4% vs 6.9%) and FBA (1.3% vs 0.5%) than men (p<0.001). Harmful drinking, after adjustment for sex and socioeconomic status, was associated with a higher prevalence of depression (OR 1.8, 95% CI 1.3 to 2.4, p<0.001), anxiety (OR 1.4, 95% CI 1.0 to 2.0, p<0.001) and FBA (OR 2.4, 95% CI 1.04 to 5.56, p=0.009) compared with lower-risk drinkers. In contrast, hazardous drinking was associated with a lower prevalence of GAD (OR 0.69, 95% CI 0.54 to 0.88) and depression (OR 0.68, 95% CI 0.54 to 0.86) compared with lower-risk drinkers.

Conclusions

Young adults in the UK who drink harmfully are more likely to have depression and other internalising disorders. Further research should test whether there is a J-shaped relationship between alcohol consumption and mental health in young people and whether this varies across the life course.
DLG5 variants are associated with multiple congenital anomalies including ciliopathy phenotypes
Authors: Marquez Jonathan , Mann Nina , Arana Kathya , Deniz Engin , Ji Weizhen , Konstantino Monica , Mis Emily K , Deshpande Charu , Jeffries Lauren , McGlynn Julie , Hugo Hannah , Widmeier Eugen , Konrad Martin , Tasic Velibor , Morotti Raffaella , Baptista Julia , Ellard Sian , Lakhani Saquib Ali , Hildebrandt Friedhelm , Khokha Mustafa K
Published: July 2020

Background

Cilia are dynamic cellular extensions that generate and sense signals to orchestrate proper development and tissue homeostasis. They rely on the underlying polarisation of cells to participate in signalling. Cilia dysfunction is a well-known cause of several diseases that affect multiple organ systems including the kidneys, brain, heart, respiratory tract, skeleton and retina.

Methods

Among individuals from four unrelated families, we identified variants in discs large 5 (DLG5) that manifested in a variety of pathologies. In our proband, we also examined patient tissues. We depleted dlg5 in Xenopus tropicalis frog embryos to generate a loss-of-function model. Finally, we tested the pathogenicity of DLG5 patient variants through rescue experiments in the frog model.

Results

Patients with variants of DLG5 were found to have a variety of phenotypes including cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations. We also observed a loss of cilia in cystic kidney tissue of our proband. Knockdown of dlg5 in Xenopus embryos recapitulated many of these phenotypes and resulted in a loss of cilia in multiple tissues. Unlike introduction of wildtype DLG5 in frog embryos depleted of dlg5, introduction of DLG5 patient variants was largely ineffective in restoring proper ciliation and tissue morphology in the kidney and brain suggesting that the variants were indeed detrimental to function.

Conclusion

These findings in both patient tissues and Xenopus shed light on how mutations in DLG5 may lead to tissue-specific manifestations of disease. DLG5 is essential for cilia and many of the patient phenotypes are in the ciliopathy spectrum.