bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrition interventions for body composition, physical function, cognition in hospitalized older adults: A systematic review of individuals 75 years and older
Authors: Dowling Lisa , Lynch David H. , Batchek Dakota , Sun Chang , Mark‐Wagstaff Charlotte , Jones Emily , Prochaska Micah , Huisingh‐Sheetz Megan , Batsis John A.
Published: February 2024

Background

Globally, the oldest old population is expected to triple by 2050. Hospitalization and malnutrition can result in progressive functional decline in older adults. Minimizing the impact of hospitalization on functional status in older adults has the potential to maintain independence, reduce health and social care costs, and maximize years in a healthy state. This study aimed to systematically review the literature to identify nutritional interventions that target physical function, body composition, and cognition in the older population (≥ 75 years).

Methods

A systematic review was conducted to evaluate the efficacy of nutritional interventions on physical function, body composition, and cognition in adults aged ≥ 75 years or mean age ≥80 years. Searches of PubMed (National Institutes of Health, National Library of Medicine), Scopus (Elsevier), EMBASE (Elsevier), Cumulative Index to Nursing and Allied Health Literature (CINAHL) with Full Text (EBSCOhost), and PsycInfo (EBSCOhost) were conducted. Screening, data extraction, and quality assessment were performed in duplicate and independently (CRD42022355984; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=355984).

Results

Of 8311 citations identified, 2939 duplicates were excluded. From 5372 citations, 189 articles underwent full‐text review leaving a total of 12 studies for inclusion. Interventions were food‐based, protein‐based, carbohydrate‐based, personalized, or used parenteral nutrition. Ten studies monitored anthropometric or body composition changes with three showing maintenance or improvements in lean mass, body mass index, triceps skinfold, and mid‐upper arm circumference compared with the control group. Six studies monitored physical function but only the largest study found a beneficial effect on activities of daily living. Two of three studies showed the beneficial effects of nutritional intervention on cognition.

Conclusion

There are few, high‐quality, nutrition‐based interventions in older adults ≥75 years. Despite heterogeneity, our findings suggest that large, longer‐term (>2 weeks) nutritional interventions have the potential to maintain body composition, physical function, and cognition in adults aged 75 years and older during hospitalization.
Adolescents' belonging in post‐divorce families: Examining residential and digital contact with mothers and fathers
Authors: Rejaän Zoë , van der Valk Inge E. , Branje Susan
Published: February 2024

Using data of 166 adolescents from divorced families, this study examined longitudinal associations between the quantity and quality of adolescents’ residential contact and digital contact with parents, and their sense of family belonging. Cross‐lagged panel models showed concurrent associations among adolescents’ residential and digital contact with each parent, yet positively for fathers and negatively for mothers. Some cross‐lagged paths revealed that higher‐quality interactions may contribute to positive changes in contact. Although there were effects of parent‐adolescent contact on family belongingness, over time belongingness was mostly predicted by the general quality of contact. The results suggest that post‐divorce relationships require frequent and meaningful time together, the effects of which, however, do hardly transfer over time in terms of adolescents’ belongingness.
Sleep timing behaviour, sleep duration and adherence to obesogenic dietary patterns from pre‐school to school age: results from the Portuguese birth cohort Generation XXI
Authors: Vilela Sofia , Vaz Andreia , Oliveira Andreia
Published: February 2024

In an obesogenic environment, short sleeping may increase opportunistic eating. The timing of sleep might also influence the drive to eat. This study investigated the prospective association of sleep timing and duration with diet in 5286 children from the Portuguese birth cohort Generation XXI, evaluated at 4 and 7 years of age. At 4 years, sleep duration was categorised into ≤10 and >10 h. Four sleep timing categories were generated based on the median split for sleep‐onset and ‐offset times: ‘Early Sleep‐Early Wake’; ‘Early Sleep‐Late Wake’; ‘Late Sleep‐Early Wake’; ‘Late Sleep‐Late Wake’. At 7 years, diet was obtained by a food frequency questionnaire and three dietary patterns were included: ‘Healthier’, ‘Energy‐Dense Foods (EDF)’ and ‘Snacking’. The Healthy Eating Index was used to evaluate diet quality. Multinomial logistic regression models and generalised linear models were performed. Children who had a late sleep, independently of the time of waking up, had higher odds of following the ‘EDF’ pattern, compared with the ‘Healthier’. Boys who had late sleep and/or late wake had also higher odds of following the ‘Snacking’ pattern and had poorer diet quality. In both sexes, a late sleep or late wake were associated with a lower diet quality, compared to the group ‘Early Sleep‐Early Wake’, and independently of nap behaviour. In boys, shorter sleep duration was associated with a poorer diet. In conclusion, pre‐schoolers with late bedtimes or wake‐up times have worse dietary patterns and poorer diet quality at the age of 7 years, which seems to be independent of sleep duration.
Real‐world economic burden of hepatitis C and impact of direct‐acting antivirals in France: A nationwide claims data analysis
Authors: Lam Laurent , Carrieri Patrizia , Hejblum Gilles , Bellet Jonathan , Bourlière Marc , Carrat Fabrice
Published: February 2024

Background and Aims

The economic impact of managing patients with hepatitis C virus (HCV) infection remains unknown. This study aimed to assess the economic burden of chronic HCV infection from a national health insurance perspective and the impact of direct‐acting antivirals (DAAs) using nationwide real‐world data.

Methods

Patients with chronic HCV infection were identified from the French Health Insurance Claims Databases (SNDS) and matched for age and sex to the general population. Health resource utilization and reimbursements were summarized according to healthcare expenditure items from 2012 to 2021. The economic burden attributable to chronic HCV infection was evaluated over a 10‐year period. Finally, the impact of DAAs was estimated using economic data derived from the SNDS.

Results

A total of 145 187 patients with chronic HCV infection were identified. Among the patients eligible for DAA therapy, 81.5% had received DAA by the end of 2021. Over a 10‐year period, managing patients with chronic HCV infection resulted in an additional cost of €9.71 billion (95% confidence interval [CI]: €9.66–€9.78 billion) or €9191 (95% CI: €9134–€9252) per patient per year compared to the general population. After DAA therapy, patients with chronic HCV infection had a higher economic burden than the general population, with an additional cost of €5781 (95% CI: €5540–€6028) per patient at the fifth‐year post‐DAA therapy.

Conclusions

A significant economic burden persists among patients with HCV infection after DAA treatment. The high proportion of patients not treated with DAA therapy supports reinforcing policies for universal access.
Unfolding language awareness in a plurilingual context: A study of metalinguistic, practical, and critical language awareness
Authors: Krogager Andersen Line
Published: February 2024

As part of a larger project investigating language awareness in plurilingual settings across educational levels through a multiple case study, this article zooms in on students’ language awareness as it unfolds in a classroom in a Danish upper secondary school, in the context of a compulsory, plurilingual general language awareness course. Considering language awareness as a sociocognitive phenomenon that may meaningfully be observed through students’ engagement with language in the classroom, qualitative data were collected through observation, interviews, and collections of student work, and analyzed using an abductive form of qualitative content analysis. The initial deductive analysis is based on a theoretical model of language awareness; additional, inductive analyses lead to more nuanced descriptions of students’ metalinguistic, practical, and critical language awareness. Finally, a contextualized analysis of one example is given to illustrate the collaborative unfolding of language awareness in this context, leading to the conclusion that the different forms of language awareness studied are often interlinked and that they should be viewed as such both in research and teaching practice.
Cone allometry and seed protection from fire are similar in serotinous and nonserotinous conifers
Authors: Greene David F. , Kane Jeffrey M. , Pounden Edith , Michaletz Sean T.
Published: February 2024

Serotiny is an adaptive trait that allows certain woody plants to persist in stand‐replacing fire regimes. However, the mechanisms by which serotinous cones avoid seed necrosis and nonserotinous species persist in landscapes with short fire cycles and serotinous competitors remain poorly understood.

To investigate whether ovulate cone traits that enhance seed survival differ between serotinous and nonserotinous species, we examined cone traits in 24 species within Pinaceae and Cupressaceae based on physical measurements and cone heating simulations using a computational fluid dynamics model.

Fire‐relevant cone traits were largely similar between cone types; those that differed (e.g. density and moisture) conferred little seed survival advantage under simulated fire. The most important traits influencing seed survival were cone size and seed depth within the cone, which was found to be an allometric function of cone mass for both cone types.

Thus, nonserotinous cones should not suffer significantly greater seed necrosis than serotinous cones of equal size. Closed nonserotinous cones containing mature seeds may achieve substantial regeneration after fire if they are sufficiently large relative to fire duration and temperature. To our knowledge, this is the most comprehensive study of the effects of fire‐relevant cone traits on conifer regeneration supported by physics‐based fire simulation.
Willingness‐to‐pay for the conservation of endangered frog species in Taiwan
Authors: Velasco Jerald M. , Tseng Wei‐Chun , Chang Yi‐Hsuan , Chiueh Ya‐Wen , Liu Wan‐Yu , Chang Chia‐Lin
Published: February 2024

Taiwan's awareness of environmental conservation and biodiversity has been increasing in recent years. As frog plays a vital role in the environment and recreational activities in Taiwan, this study aimed to quantify the willingness‐to‐pay (WTP) of the public for conserving the selected endangered frog species. Respondents were asked using a semistructured questionnaire with auxiliary audio and video files. After deleting incomplete responses following regular data handling, 585 valid responses were used in the estimation. Using the contingent valuation method and single‐bounded dichotomous choice model, the results showed that people are willing to pay an amount of 32.01 USD (922.85 New Taiwan Dollars) per person annually. Factors affecting the public's WTP include price, age, support for establishing conservation areas, payment through donations, number of trips in ecotourism, and the place of residency in Taiwan. The result of this study can be used as a benchmark for the government for the implementation of the conservation and rehabilitation of the habitat of the endangered frog species in the future.
Flower‐visitor and pollen‐load data provide complementary insight into species and individual network roles
Authors: Cirtwill Alyssa R. , Wirta Helena , Kaartinen Riikka , Ballantyne Gavin , Stone Graham N. , Cunnold Helen , Tiusanen Mikko , Roslin Tomas
Published: February 2024

Most animal pollination results from plant–insect interactions, but how we perceive these interactions may differ with the sampling method adopted. The two most common methods are observations of visits by pollinators to plants and observations of pollen loads carried by insects. Each method could favour the detection of different species and interactions, and pollen load observations typically reveal more interactions per individual insect than visit observations. Moreover, while observations concern plant and insect individuals, networks are frequently analysed at the level of species. Although networks constructed using visitation and pollen‐load data have occasionally been compared in relatively specialised, bee‐dominated systems, it is not known how sampling methodology will affect our perception of how species (and individuals within species) interact in a more generalist system. Here we use a Diptera‐dominated high‐Arctic plant–insect community to explore how sampling approach shapes several measures of species' interactions (focusing on specialisation), and what we can learn about how the interactions of individuals relate to those of species. We found that species degrees, interaction strengths, and species motif roles were significantly correlated across the two method‐specific versions of the network. However, absolute differences in degrees and motif roles were greater than could be explained by the greater number of interactions per individual provided by the pollen‐load data. Thus, despite the correlations between species roles in networks built using visitation and pollen‐load data, we infer that these two perspectives yield fundamentally different summaries of the ways species fit into their communities. Further, individuals' roles generally predicted the species' overall role, but high variability among individuals means that species' roles cannot be used to predict those of particular individuals. These findings emphasize the importance of adopting a dual perspective on bipartite networks, as based on the different information inherent in insect visits and pollen loads.
Ion channel dysfunction and fibrosis in atrial fibrillation: Two sides of the same coin
Authors: Arabia Gianmarco , Bellicini Maria Giulia , Cersosimo Angelica , Memo Maurizio , Mazzarotto Francesco , Inciardi Riccardo Maria , Cerini Manuel , Chen Lin Yee , Aboelhassan Mohamed , Benzoni Patrizia , Mitacchione Gianfranco , Bontempi Luca , Curnis Antonio
Published: February 2024

Background

Atrial fibrillation (AF) is a common heart rhythm disorder that is associated with an increased risk of stroke and heart failure (HF). Initially, an association between AF and ion channel dysfunction was identified, classifying the pathology as a predominantly electrical disease. More recently it has been recognized that fibrosis and structural atrial remodeling play a driving role in the development of this arrhythmia also in these cases.

Purpose

Understanding the role of fibrosis in genetic determined AF could be important to better comprise the pathophysiology of this arrhythmia and to refine its management also in nongenetic forms. In this review we analyze genetic and epigenetic mechanisms responsible for AF and their link with atrial fibrosis, then we will consider analogies with the pathophysiological mechanism in nongenetic AF, and discuss consequent therapeutic options.
Routes to relevance: Philosophies of relevant logics
Authors: Standefer Shawn
Published: February 2024

Relevant logics are a family of non‐classical logics characterized by the behavior of their implication connectives. Unlike some other non‐classical logics, such as intuitionistic logic, there are multiple philosophical views motivating relevant logics. Further, different views seem to motivate different logics. In this article, we survey five major views motivating the adoption of relevant logics: Use Criterion, sufficiency, meaning containment, theory construction, and truthmaking. We highlight the philosophical differences as well as the different logics they support. We end with some questions for future research.
Carbon dioxide emissions and environmental risks: Long term and short term
Authors: Boubaker Sabri , Liu Zhenya , Mu Yuhao , Zhan Yaosong
Published: February 2024

The world is currently experiencing the environmental challenge of global warming, necessitating careful planning of carbon dioxide (CO2) emissions to deal with this problem. This study examines the environmental challenge posed by CO2 emissions from both a long and short‐term perspective. In the long term, despite efforts made by countries, our change‐point detection analysis shows that there has been no structural change in CO2 emissions since 1950. Without significant efforts, the carbon budget corresponding to the Paris Agreement's target will be exhausted by 2046. To achieve this target, a significant reduction in global CO2 emissions of 3.22% per year is necessary. In the short term, COVID‐19 is thought to have relieved pressure on CO2 emissions. However, this study shows that CO2 emissions quickly returned to normal levels after a brief downturn, and we provide information on the order of CO2 emissions recovery for different sectors.
Asymptotic profiles of a spatial vector‐borne disease model with Fokker–Planck‐type diffusion
Authors: Wang Kai , Zhao Hongyong , Wang Hao
Published: February 2024

This paper is concerned with a spatially heterogeneous vector‐borne disease model that follows the Fokker–Planck‐type diffusion law. One of the significant features in our model is that Fokker–Planck‐type diffusion is used to characterize individual movement, which poses new challenges to theoretical analysis. We derive for the first time the variational characterization of basic reproduction ratio for the model under certain conditions and investigate its asymptotic profiles with respect to the diffusion rates. Furthermore, via overcoming the difficulty of the associated elliptic eigenvalue problem, the asymptotic behaviors of endemic equilibrium for the model are discussed. Our results imply that whether rapid or slow movement of susceptible and infected individuals are conducive to disease control depends on the degree of disease risk in the habitat. Numerically, we verify the theoretical results and detect that Fokker–Planck‐type diffusion may amplify the scale of disease infection, which in turn increases the complexity of disease transmission by comparing the impacts of distinct dispersal types on disease dynamics.
Aesthetic oral rehabilitation of the upper‐anterior sector with supra‐nano filling resin in a patient with woolly hair syndrome: case report
Authors: Conto Quispe Patricia Nataly , Tapia Martinez Akemy Celeste , Vilcapoma Guerra Henry Jesús , Lavado García Lenny , Torres Ramos Gilmer
Published: February 2024

Background

Woolly Hair Syndrome (WHS) is a rare birth condition that affects the structure of hair in non‐black people. The pathogenesis is not yet defined. It is postulated that the hair follicle's desmosomes (specifically desmoplaquine, placoglobin and placofilin‐1, which are cell structural proteins that keep the adhesion among close cells) would be altered in this pathology, leading to fragility in the cellular union. It is subdivided into two large groups: the localized or circumscribed variant and the generalized variant. From birth or first months of life, patients with WHS are clinically characterized by the presence of a portion or entire scalp area of very short frizzy hair, usually of a smaller diameter, brittle and lighter color. The most frequent skin manifestations are pilar keratosis and palmo‐plantar keratodermia. The diagnosis is based on the clinical findings, and it is facilitated by trichotoscopic examination. However, a definitive diagnosis of WHS requires genetic testing. Oral agenesis, enamel defects (such as hypomineralization), atypical caries, dental inclusion, and malformed pin‐shaped teeth may occur.

Objective

To describe an aesthetic alternative of oral rehabilitation using the mock‐up technique in a patient with WHS.

Clinical case

A 5‐year‐old female patient diagnosed with WHS from the National Institute of Child Health

Nihch

Breña, Lima, who was referred from the Genetic service to the Pediatric Dentistry service in order to screen outbreaks of infection associated with odontogenic origin and dental anomalies. At the ectoscopy, a patient with short capillary length, brittle and curly hair, dry skin, and nail dystrophy was observed. At the intraoral clinical examination, anterior pieces of 52, 51, 61, 62, and enamel hypomineralization were observed in all teeth. The radiographic examination showed agenesis of parts 41, 34, and 45. Integral dental treatment was performed in the operating room under general anesthesia due to the complexity of the case. Pulpectomy in pieces 52, 51, 61, 62, post of composite resin, and rehabilitation with supra‐nanow filling resin using the mock‐up technique were proposed as alternative treatments.

Conclusion

The making of supra‐nano filling resin‐based crowns using the mock‐up technique is an alternative treatment for aesthetic oral rehabilitation in deciduous dentition of patients with WHS. The aesthetic treatment was achieved using supra nano‐filling resins. After 12 months of dental treatment, a favorable response was observed, improving the chewing, phonation and aesthetics of the patient.
Too Privileged to Move? Neighbourhood Perception and Relocation Intention in China's Gated Communities
Authors: Li Chenxi , He Shenjing
Published: February 2024

The association between neighbourhood characteristics and residential relocation is a classic topic in urban studies. In China, where gated communities (GCs) have become a highly popular residential form, how and to what extent residents’ perceptions of GCs affect their relocation intention has not been quantitatively examined. Drawing on a large‐scale household survey conducted in Shanghai, we use multi‐level logistic regression models to examine the impact of the perceptions of neighbourhood environment, attachment and gatedness on relocation intention. Our findings are threefold: (1) the greater the perceived improvement of the neighbourhood environment, the lower the likelihood of relocation intention; (2) respondents with higher levels of neighbourhood attachment tend to have lower relocation intention and (3) respondents living in neighbourhoods with higher levels of gatedness are less likely to have relocation intention. This research contributes to the literature of neighbourhood studies and GCs by quantifying the ramification of entrenched ‘gated mindset’ in urban China.
Current management of SARS‐CoV‐2 infection in solid organ transplant recipients: Experience derived from an ESGICH–ESOT survey
Authors: Visentin Alessandro , Pickavance Elise , San‐Juan Rafael , Grossi Paolo Antonio , Manuel Oriol , Aguado Jose M.
Published: February 2024

Objective

Solid organ transplant (SOT) recipients have a poorer SARS‐CoV‐2 vaccine response and higher risk for COVID‐19‐associated complications. However, there is no consensus on the current management of COVID‐19 and data on persistent COVID‐19 rates in SOT recipients are lacking.

Methods

An electronic survey concerning the management of COVID‐19 in SOT recipients was distributed among all members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) and of the European Society for Organ Transplantation (ESOT). Four major sections were covered: prevention, early COVID‐19, late COVID‐19, and persistent COVID‐19. We developed a structured questionnaire including eight multiple‐choice questions with branching logic in case of positive answers and three open‐ended questions related to clinical practice. Questions were asked separately for lung and non‐lung transplantation.

Results

Thirty‐two physicians from 24 different centers participated. Most answers (n = 30) were provided by European physicians. Thirty of 32 (93.75%) physicians managed non‐lung transplant recipients and 12 of 32 (33.3%) lung transplant recipients. There was a huge variability in practice regarding the treatment of COVID‐19, and particularly noticeable when considering lung and non‐lung transplant recipients. Main discordances included the use of nirmatrelvir alone or in combination therapy for early COVID‐19, the use of immunomodulatory drugs other than steroids for late COVID‐19, and the need for treating asymptomatic viral shedding in persistent COVID‐19. There was more similarity in terms of prophylaxis recommendations.

Conclusion

Despite a low number of respondents, this survey shows that there are many differences on how experts manage SARS‐CoV‐2 infections in SOT recipients.

image
Alternative Approach for Thermo-Hydraulic Modeling of Direct Steam Generation in Parabolic Trough Solar Collectors
Authors: González-Mora Eduardo , Durán-García M. Dolores
Published: February 2024

The implementation of direct steam generation in linear concentrators is limited mainly by the complexity and the high demand for computational resources of the models developed to predict the installation behavior. With this in mind, we introduce an innovative methodology to characterize the thermo-hydraulic behavior of direct steam generation in parabolic trough solar collectors, with a strong focus on two-phase flow phenomena. Our proposed approach has resulted in a generalized function that eliminates the need for the convective coefficient h and enables accurate prediction of the flow pattern within the receiver. By comparing our model with experimental data from the literature, we achieved relative squared errors (RSEs) values of less than 3% for temperature and pressure calculations, thus validating the robustness of our methodology. The Taitel and Dukler diagram confirms an appropriate flow pattern, while intermittent flow is observed initially during boiling; the pressure drop, although slightly elevated compared to direct solar steam (DISS) loop results, remains within acceptable limits; and the model demonstrates suitability for assessing liquid water, phase change, and superheated steam temperature evolution along the loop. Moreover, we further showcased the practical application of our developed model by applying it to a specific case study conducted in Agua Prieta, Sonora (Northwest México). The validated model exhibits versatility and is applicable to various cases, including both concentrating systems for electricity production and solar heat for industrial processes.
Sonic boom propagation in urban canyons using a combined ray tracing/radiosity method
Authors: Riegel Kimberly , Sparrow Victor W.
Published: February 2024

Sonic boom propagation over land is being studied to ensure a minimal impact on the population in the event that supersonic flight over land becomes permissible. Sonic boom behavior in and around urban areas is particularly important due to the high density of people residing in cities and the increased probability of impacting large numbers of people if urban areas lie in the flight path. This study models sonic booms around urban canyons using a combined ray tracing/radiosity method. The impacts of several parameters, such as diffusion, arrival angle, building heights, and canyon width, on the sound field were explored. The results showed that without diffusion, there was no real trend as the canyon height and width and arrival angles were varied. There were strong shadow zones where no sound was detected as this model does not include diffraction. In other locations, between one and four boom events were received. The resulting perceived level in dB (PLdB) varied from 0 in the shadow zones to 94 dB. Diffuse reflections was the parameter that had the greatest impact on the resulting signatures. Parameters that caused an increased number of reflections showed significant changes in the signature shape and a dramatic reduction in the PLdB.
Comparison of Sleep and Physical Activity Metrics From Wrist-Worn ActiGraph wGT3X-BT and GT9X Accelerometers During Free-Living in Adults
Authors: Buchan Duncan S.
Published: February 2024

Background: ActiGraph accelerometers can monitor sleep and physical activity (PA) during free-living, but there is a need to confirm agreement in outcomes between different models. Methods: Sleep and PA metrics from two ActiGraphs were compared after participants (N = 30) wore a GT9X and wGT3X-BT on their nondominant wrist for 7 days during free-living. PA metrics including total steps, counts, average acceleration—Euclidean Norm Minus One (ENMO) and Mean Amplitude Deviation, intensity gradient, the minimum acceleration value of the most active 10 and 30 min (M10, M30), time spent in activity intensities from vector magnitude (VM) counts, and ENMO cut points and sleep metrics (sleep period time window, sleep duration, sleep onset, and waking time) were compared. Results: Excellent agreement was evident for average acceleration-Mean Amplitude Deviation, counts, total steps, M10, and light PA (VM counts) with good agreement evident from the remaining PA metrics apart from moderate–vigorous PA (VM counts) which demonstrated moderate agreement. Mean bias for all PA metrics were low, as were the limits of agreement for the intensity gradient, average acceleration-Mean Amplitude Deviation, and inactive time (ENMO and VM counts). The limits of agreement for all other PA metrics were >10%. Excellent agreement, low mean bias, and narrow limits of agreement were evident for all sleep metrics. All sleep and PA metrics demonstrated equivalence (equivalence zone of ≤10%) apart from moderate–vigorous PA (ENMO) which needed an equivalence zone of 16%. Conclusions: Equivalent estimates of almost all PA and sleep metrics are provided from the GT9X and wGT3X-BT worn on the nondominant wrist.
Phage-antibiotic synergy against daptomycin-nonsusceptible MRSA in an
ex vivo
simulated endocardial pharmacokinetic/pharmacodynamic model
Authors: Kunz Coyne Ashlan J. , Bleick Callan , Stamper Kyle , Kebriaei Razieh , Bayer Arnold S. , Lehman Susan M. , Rybak Michael J.
Published: February 2024

Phage-antibiotic combinations (PAC) offer a potential solution for treating refractory daptomycin-nonsusceptible (DNS) methicillin-resistant
Staphylococcus aureus
(MRSA) infections. We examined PAC activity against two well-characterized DNS MRSA strains (C4 and C37)
in vitro
and
ex vivo
. PACs comprising daptomycin (DAP) ± ceftaroline (CPT) and a two-phage cocktail (Intesti13 + Sb-1) were evaluated for phage-antibiotic synergy (PAS) against high MRSA inoculum (10
9
CFU/mL) using (i) modified checkerboards (CB), (ii) 24-h time-kill assays (TKA), and (iii) 168-h
ex vivo
simulated endocardial vegetation (SEV) models. PAS was defined as a fractional inhibitory concentration ≤0.5 in CB minimum inhibitory concentration (MIC) or a ≥2 log
10
CFU/mL reduction compared to the next best regimen in time-kill assays and SEV models. Significant differences between regimens were assessed by analysis of variance with Tukey’s post hoc modification (α = 0.05). CB assays revealed PAS with Intesti13 + Sb-1 + DAP ± CPT. In 24-h time-kill assays against C4, Intesti13 + Sb-1 + DAP ± CPT demonstrated synergistic activity (−Δ7.21 and −Δ7.39 log
10
CFU/mL, respectively) (
P
< 0.05 each). Against C37, Intesti13 + Sb-1 + CPT ± DAP was equally effective (−Δ7.14 log
10
CFU/mL each) and not significantly different from DAP + Intesti13 + Sb-1 (−Δ6.65 log
10
CFU/mL). In 168-h SEV models against C4 and C37, DAP ± CPT + the phage cocktail exerted synergistic activities, significantly reducing bio-burdens to the detection limit [2 log
10
CFU/g (−Δ7.07 and −Δ7.11 log
10
CFU/g, respectively)] (
P
< 0.001). At 168 h, both models maintained stable MICs, and no treatment-emergent phage resistance occurred with DAP or DAP + CPT regimens. The two-phage cocktail demonstrated synergistic activity against two DNS MRSA isolates in combination with DAP + CPT
in vitro
and
ex vivo
. Further
in vivo
PAC investigations are needed.
Listeria
adhesion protein orchestrates caveolae-mediated apical junctional remodeling of epithelial barrier for
Listeria monocytogenes
translocation
Authors: Drolia Rishi , Bryant Donald B. , Tenguria Shivendra , Jules-Culver Zuri A. , Thind Jessie , Amelunke Breanna , Liu Dongqi , Gallina Nicholas L. F. , Mishra Krishna K. , Samaddar Manalee , Sawale Manoj R. , Mishra Dharmendra K. , Cox Abigail D. , Bhunia Arun K.
Published: February 2024

The cellular junctional architecture remodeling by
Listeria
adhesion protein-heat shock protein 60 (LAP-Hsp60) interaction for
Listeria monocytogenes
(
Lm
) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate that
Lm
crosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (
lap
−
or Δ
inlA
) or double (
lap
−
Δ
inlA
) mutant strains show significant defects. LAP promotes
Lm
translocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA facilitates
Lm
translocation at cells displaying apical E-cadherin during cell extrusion and mucus expulsion from goblet cells. LAP hijacks caveolar endocytosis to traffic integral junctional proteins to the early and recycling endosomes. Pharmacological inhibition in a cell line and genetic knockout of caveolin-1 in mice prevents LAP-induced intestinal permeability, junctional endocytosis, and
Lm
translocation. Furthermore, LAP-Hsp60-dependent tight junction remodeling is also necessary for InlA access to E-cadherin for
Lm
intestinal barrier crossing in InlA-permissive hosts.

IMPORTANCE

Listeria monocytogenes
(
Lm
) is a foodborne pathogen with high mortality (20%–30%) and hospitalization rates (94%), particularly affecting vulnerable groups such as pregnant women, fetuses, newborns, seniors, and immunocompromised individuals. Invasive listeriosis involves
Lm
’s internalin (InlA) protein binding to E-cadherin to breach the intestinal barrier. However, non-functional InlA variants have been identified in
Lm
isolates, suggesting InlA-independent pathways for translocation. Our study reveals that
Listeria
adhesion protein (LAP) and InlA cooperatively assist
Lm
entry into the gut lamina propria in a gerbil model, mimicking human listeriosis in early infection stages. LAP triggers caveolin-1-mediated endocytosis of critical junctional proteins, transporting them to early and recycling endosomes, facilitating
Lm
passage through enterocytes. Furthermore, LAP-Hsp60-mediated junctional protein endocytosis precedes InlA’s interaction with basolateral E-cadherin, emphasizing LAP and InlA’s cooperation in enhancing
Lm
intestinal translocation. This understanding is vital in combating the severe consequences of
Lm
infection, including sepsis, meningitis, encephalitis, and brain abscess.
DDX4 enhances antiviral activity of type I interferon by disrupting interaction of USP7/SOCS1 and promoting degradation of SOCS1
Authors: Miao Ying , Zhang Tingting , Guan Mingcheng , Zhao Qian , Zhang Renxia , Liu Xuyi , Ma Tianrun , Ren Tengfei , Zheng Zhijin , He Wei , Tian Wanying , Cui Qun , Zhai Xingyu , Zuo Yibo , Zhu Hong , Zheng Hui , Yuan Yukang
Published: February 2024

DEAD-box helicase (DDX) family members play differential roles in regulating innate antiviral immune response. However, the physiological roles played by DDX4 in antiviral innate immunity remain unclear. In this study, we unveiled that DDX4 acts as a positive regulatory molecule of Type-I interferon (IFN-I)-mediated antiviral activity. Our findings demonstrate that IFN-I upregulates DDX4 protein levels, and subsequently, overexpression of DDX4 enhances the IFN-I-mediated signaling pathway. This creates a positive feedback loop that amplifies the antiviral response. DDX4 was found to bind with deubiquitinase ubiquitin-specific protease 7 (USP7), leading to the disruption of the interaction between USP7 and suppressor of cytokine signaling 1 (SOCS1) and the subsequent degradation of SOCS1. This process enhances the antiviral function of IFN-I. Our findings provide new insights into the regulatory role of DDX4 in the IFN-I response.

IMPORTANCE

DDX4, identified as a putative RNA helicase that modulates RNA secondary structure through RNA binding, is primarily acknowledged for its role in regulating mRNA translation within the germline. Nevertheless, the extent of DDX4’s involvement in the antiviral innate immune response remains largely unexplored. This study presents evidence of a previously unrecognized positive feedback loop between DDX4 and the antiviral response, suggesting that disruption of this loop may serve as a novel mechanism for viral evasion. Furthermore, our findings elucidate a positive regulatory mechanism by which the DDX4/USP7/SOCS1 axis mediates the antiviral activity of Type-I interferon, which provides new insight into strategies for improving the efficacy of IFN-based antiviral therapy.
Investigating the impact of antibiotic-induced dysbiosis on protection from
Clostridium difficile
colitis by mouse colonic innate lymphoid cells
Authors: Uddin Md Jashim , Thompson Brandon , Leslie Jhansi L. , Fishman Casey , Sol-church Katia , Kumar Pankaj , Petri William A.
Published: February 2024

Innate lymphoid cells (ILCs) play a critical role in maintaining intestinal health in homeostatic and diseased conditions. During
Clostridium difficile
infection (CDI), IL-33 activates ILC2 to protect from colonic damage and mortality. The function of IL-33 and ILC is tightly regulated by the intestinal microbiota. We set out to determine the impact of antibiotic-induced disruption of the microbiome on ILC function. Our goal was to understand antibiotic-induced changes in ILC function on susceptibility to
C. difficile
colitis in a mouse model. We utilized high-throughput single-cell RNAseq to investigate the phenotypic features of colonic ILC at baseline, after antibiotic administration with or without IL-33 treatment. We identified a heterogeneous landscape of colonic ILCs with gene signatures of inflammatory, anti-inflammatory, migratory, progenitor, plastic, and antigen-presenting ILCs. Antibiotic treatment decreased ILC2 while coordinately increasing ILC1 and ILC3 phenotypes. Notably, Ifng
+
, Ccl5
+
, and Il23r
+
ILC increased after antibiotics. IL-33 treatment counteracted the antibiotic effect by downregulating ILC1 and ILC3 and activating ILC2. In addition, IL-33 treatment markedly induced the expression of type 2 genes, including Areg and Il5. Finally, we identified amphiregulin, produced by ILC2, as protective during
C. difficile
infection. Together, our data expand our understanding of how antibiotics induce susceptibility to
C. difficile
colitis through their impact on ILC subsets and function.

IMPORTANCE

Clostridium difficile
infection (CDI) accounts for around 500,000 symptomatic cases and over 20,000 deaths annually in the United States alone. A major risk factor of CDI is antibiotic-induced dysbiosis of the gut. Microbiota-regulated IL-33 and innate lymphoid cells (ILCs) are important in determining the outcomes of
C. difficile
infection. Understanding how antibiotic and IL-33 treatment alter the phenotype of colon ILCs is important to identify potential therapeutics. Here, we performed single-cell RNAseq of mouse colon ILCs collected at baseline, after antibiotic treatment, and after IL-33 treatment. We identified heterogeneous subpopulations of all three ILC subtypes in the mouse colon. Our analysis revealed several potential pathways of antibiotic-mediated increased susceptibility to intestinal infection. Our discovery that Areg is abundantly expressed by ILCs, and the protection of mice from CDI by amphiregulin treatment, suggests that the amphiregulin-epidermal growth factor receptor pathway is a potential therapeutic target for treating intestinal colitis.
A novel thermophilic strain of
Bacillus subtilis
with antimicrobial activity and its potential application in solid-state fermentation of soybean meal
Authors: Qi Nanshan , Zhan Xiaoshu , Milmine Joshua , Chang Kai-Hsiang , Li Julang
Published: February 2024

Soybean meal (SBM) is the most important source of plant protein in animal feeds, containing around 41%–48% crude protein. Nevertheless, 70%–80% of these proteins is allergenic antigens that can have adverse implications for the gastrointestinal well-being of animals, especially to young animals. Microbial fermentation is one of the most cost-effective strategies used to reduce allergenic antigens from plant sources. In this study, we report the isolation and characterization of a novel probiotic
Bacillus subtilis
“L5” strain from lake mud. L5 demonstrated remarkable temperature tolerance across a broad temperature spectrum, thriving at 25°C, 37°C, and 50°C. In addition, antimicrobial assay revealed that L5 exhibits strong antimicrobial activity against
Escherichia coli
, effectively reducing or eliminating the growth of Gram-negative bacteria in SBM when fermented with L5. When applied to SBM fermentation, L5 efficiently reduced SBM antinutritional factors such as glycinin, β-conglycinin, trypsin inhibitor, phytic acid, neutral detergent fiber, and acid detergent fiber, which in turn results in an increase in crude protein content and the free amino acid concentration. Our findings on the probiotic and fermentation capabilities of L5 suggest that this novel bacterium has dual functions that make it a strong candidate for improving the nutrient values of feed via its role in fermentation.

IMPORTANCE

Soybean meal (SBM), containing 41%–48% crude protein, is the most important source of plant protein in animal feeds. Unfortunately, 70%–80% of the proteins in SBM is allergenic antigens including trypsin inhibition, β-conglycinin, and conglycinin, which negatively affect intestine health and function. Microbial solid-state fermentation methods have been applied to animal feeds for decades, to eliminate antinutritional factors. Here, a novel potential probiotic
Bacillus subtilis
“L5” strain with high enzymatic activity and antimicrobial activity will be a great help to improve the quality and reproducibility of SBM fermentation.
Conditioner application improves bedding quality and bacterial composition with potential beneficial impacts for dairy cow’s health
Authors: Duniere Lysiane , Frayssinet Bastien , Achard Caroline , Chevaux Eric , Plateau Julia
Published: February 2024

Recycled manure solids (RMS) is used as bedding material in cow housing but can be at risk for pathogens development. Cows spend several hours per day lying down, contributing to the transfer of potential mastitis pathogens from the bedding to the udder. The effect of a bacterial conditioner (Manure Pro, MP) application was studied on RMS-bedding and milk qualities and on animal health. MP product was applied on bedding once a week for 3 months. Bedding and teat skin samples were collected from Control and MP groups at D01, D51, and D90 and analyzed through 16S rRNA amplicon sequencing. MP application modified bacterial profiles and diversity. Control bedding was significantly associated with potential mastitis pathogens, while no taxa of potential health risk were significantly detected in MP beddings. Functional prediction identified enrichment of metabolic pathways of agronomic interest in MP beddings. Significant associations with potential mastitis pathogens were mainly observed in Control teat skin samples. Finally, significantly better hygiene and lower Somatic Cell Counts in milk were observed for cows from MP group, while no group impact was observed on milk quality and microbiota. No dissemination of MP strains was observed from bedding to teats or milk.

IMPORTANCE

The use of Manure Pro (MP) conditioner improved recycled manure solids-bedding quality and this higher sanitary condition had further impacts on dairy cows' health with less potential mastitis pathogens significantly associated with bedding and teat skin samples of animals from MP group. The animals also presented an improved inflammation status, while milk quality was not modified. The use of MP conditioner on bedding may be of interest in controlling the risk of mastitis onset for dairy cows and further associated costs.
Abstracts from international emergency medicine journals
Authors: Production EMJ
Published: February 2024

Editor’s note: EMJ has partnered with the journals of multiple international emergency medicine societies to share from each a highlighted research study, as selected by their editors. This edition will feature an abstract from each publication.
First-in-human experience of sirolimus coated balloon for symptomatic intracranial artery stenosis
Authors: Luo Jichang , Yang Renjie , Wang Tao , Chen Jian , Lu Xia , Yang Bin , Gao Peng , Wang Yabing , Chen Yanfei , Dmytriw Adam A , Zheng Jiamin , Regenhardt Robert W , Li Zheng , Xu Han , Ma Yan , Zhao Jonathon , Jiao Liqun
Published: February 2024

Background

The drug coated balloon is a promising endovascular therapy for intracranial atherosclerosis (ICAS), potentially combining the advantages of primary angioplasty and antiproliferative drugs. Previous studies have focused on the paclitaxel coated balloon, revealing promising outcomes in the treatment of ICAS, while concerns about the neurotoxicity of paclitaxel were reported. Sirolimus was shown to have less neurotoxicity in the canine cerebral vasculature. The feasibility and safety of a sirolimus coated balloon (SCB) for ICAS have never been evaluated in humans. We assessed the first-in-human feasibility and safety of SCBs for treating symptomatic patients with severe ICAS.

Methods

This prospective, open label, single arm cohort study was designed to enroll patients with transient ischemic attacks or non-disabling, non-perforator territory ischemic stroke caused by severe ICAS (70–99%) and following at least 3 weeks after the onset of ischemic symptoms. The primary outcome was stroke or death within 30 days. All patients were followed up to detect restenosis at 6 months.

Results

A total of 60 eligible patients were enrolled with an average age of 59.4±10.8 years. The technical success rate of SCBs for ICAS was 100%. Seven patients (11.7%) required stenting because of flow limited dissections or elastic retraction. Three patients (5.0%) had 30 day strokes, including two ischemic strokes and one hemorrhagic stroke. An additional three patients had recurrent stroke or death during follow-up. Ten patients had restenosis but only two had symptoms.

Conclusions

SCBs may be feasible and safe in selected patients with symptomatic ICAS, with high grade stenosis (70–99%). Further studies are warranted.
Diagnostic accuracy of intraoperative neuromonitoring in transcarotid artery revascularization
Authors: Diogo Cinira , Na Doohwan , Sujijantarat Nanthiya , Matouk Charles , Callahan Brooke
Published: February 2024

Background

In recent years, transcarotid artery revascularization (TCAR) has emerged as a safe and effective alternative to carotid artery stenting. While intraoperative neuromonitoring (IONM) techniques such as electroencephalogram (EEG) and somatosensory evoked potentials (SSEPs) are often employed during TCAR, there is limited research on their diagnostic accuracy.

Methods

The authors retrospectively reviewed a multi-institutional IONM database of TCAR procedures performed with EEG and SSEP monitoring. A total of 516 TCAR procedures were included in this study. Significant changes in EEG and/or SSEPs, surgeon’s interventions, resolution of significant changes, and immediate postoperative neurological outcome were documented. Sensitivity, specificity, positive and negative predictive values were calculated.

Results

The incidence of intraoperative onset new neurologic deficit was 0.4%. Significant changes in EEG and/or SSEPs occurred in 5.4% of the cases. Of the cases with IONM alerts, 78.5% returned to baseline with a surgical or hemodynamic intervention. From the cases with unresolved IONM alerts, 33.3% woke up with a new neurological deficit. The overall sensitivity and specificity for IONM was 100% and 99.2%, respectively. The positive predictive value was 33.3% and the negative predictive value was 100%.

Conclusions

IONM during TCAR offers high sensitivity and specificity in predicting postoperative outcome. Patients with resolved IONM alerts had immediate neurological outcomes that were comparable to those who had no IONM alerts.