bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic recurrent multifocal osteomyelitis. A narrative and pictorial review
Authors: Sergi Consolato M. , Miller Elka , Demellawy Dina El , Shen Fan , Zhang Mingyong
Published: August 2022

Chronic recurrent and multifocal osteomyelitis (CRMO) is a nonsporadic autoinflammatory disorder. Currently, it is diagnosed based on clinical, radiologic, pathological, and longitudinal data. Numerous aspects should be highlighted due to increased knowledge in imaging and immunology. We emphasize the use of whole-body MRI, which is a non-invasive diagnostic strategy. A literature review was carried out on longitudinal studies. Commonly, the mean age at diagnosis is 11 years, ranging between 3 and 17. The most common sites are the long bone metaphysis, particularly femoral and tibial metaphysis. In addition, the pelvis, spine, clavicle, and mandible may be involved. In long bones, the radiologic appearance can show typical structure, mixed lytic and sclerotic, sclerotic or lytic. It is frequently metaphyseal or juxta-physeal, with hyperostosis or periosteal thickening. The involvement of the vertebral skeleton is often multifocal. Therefore, whole-body MRI is essential in identifying subclinical lesions. CRMO is a polymorphic disorder in which whole-body MRI is beneficial to demonstrate subclinical edema. Vertebral collapse requires long-term monitoring.
Trimethylamine-N-oxide (TMAO) mediates the crosstalk between the gut microbiota and hepatic vascular niche to alleviate liver fibrosis in nonalcoholic steatohepatitis
Authors: Zhou Dengcheng , Zhang Jing , Xiao Chengju , Mo Chunheng , Ding Bi-Sen
Published: August 2022

Liver fibrosis is one main histological characteristic of nonalcoholic steatohepatitis (NASH), a disease paralleling a worldwide surge in metabolic syndromes with no approved therapies. The role of the gut microbiota in NASH pathogenesis has not been thoroughly illustrated, especially how the gut microbiota derives metabolites to influence the distal liver in NASH. Here, we performed 16S rDNA amplicon sequencing analysis of feces from a mouse NASH model induced by a Western diet and CCl4 injury and found genera under Streptococcaceae, Alcaligenaceae, Oscillibacter, and Pseudochrobactrum, which are related metabolites of TMAO. Injection of the gut microbial metabolite TMAO reduced the progression of liver fibrosis in the mouse NASH model. Further analysis revealed that the anti-fibrotic TMAO normalized gut microbiota diversity and preserved liver sinusoidal endothelial cell integrity by inhibiting endothelial beta 1-subunit of Na (+), K (+)-ATPase (ATP1B1) expression. Collectively, our findings suggest TMAO-mediated crosstalk between microbiota metabolites and hepatic vasculature, and perturbation of this crosstalk disrupts sinusoidal vasculature to promote liver fibrosis in NASH.
Cellular heterogeneity in disease severity and clinical outcome: Granular understanding of immune response is key
Authors: Khare Kriti , Pandey Rajesh
Published: August 2022

During an infectious disease progression, it is crucial to understand the cellular heterogeneity underlying the differential immune response landscape that will augment the precise information of the disease severity modulators, leading to differential clinical outcome. Patients with COVID-19 display a complex yet regulated immune profile with a heterogeneous array of clinical manifestation that delineates disease severity sub-phenotypes and worst clinical outcomes. Therefore, it is necessary to elucidate/understand/enumerate the role of cellular heterogeneity during COVID-19 disease to understand the underlying immunological mechanisms regulating the disease severity. This article aims to comprehend the current findings regarding dysregulation and impairment of immune response in COVID-19 disease severity sub-phenotypes and relate them to a wide array of heterogeneous populations of immune cells. On the basis of the findings, it suggests a possible functional correlation between cellular heterogeneity and the COVID-19 disease severity. It highlights the plausible modulators of age, gender, comorbidities, and hosts’ genetics that may be considered relevant in regulating the host response and subsequently the COVID-19 disease severity. Finally, it aims to highlight challenges in COVID-19 disease that can be achieved by the application of single-cell genomics, which may aid in delineating the heterogeneity with more granular understanding. This will augment our future pandemic preparedness with possibility to identify the subset of patients with increased diseased severity.
In-situ radon-in-water detection for high resolution submarine groundwater discharge assessment
Authors: Zhao Shibin , Li Meng , Burnett William C. , Cheng Kai , Li Chunqian , Guo Jinjia , Yu Songling , Liu Wen , Yang Tong , Dimova Natasha T. , Chen Guangquan , Yu Zhigang , Xu Bochao
Published: August 2022

Submarine groundwater discharge (SGD), including both land-based fresh groundwater that enters the ocean from coastal aquifers as well as recirculated seawater that is continuously recharged and discharged on the seabed, has been considered as an important component of the global water and biogenic element (e.g., nitrogen, phosphorus, silicon and carbon) sources and a significant pathway for material exchange at the land-sea interface of coastal ecosystems. Some researchers reported that SGD associated nutrient additions to coastal waters have caused unwanted ecological issues, including red tides, coastal acidification and hypoxia. Natural radon isotope (222Rn, t1/2 = 3.8 d) is an excellent tracer for studying SGD and other oceanographic processes including air-sea gas exchange, sediment-water diffusion, and earthquake prediction. However, the conventional radon measurement methods suffer many technical disadvantages. We consequently developed a convenient submersible radon determination approach (“OUC-Rn”) using a commercial pulsed ionization chamber (PIC) radon sensor and gas extraction membrane module to produce high precision and high resolution observations. We demonstrate the radon degassing efficiency of the membrane contactor is comparable to the shower-head type air-water exchanger but is independent of operating position. The radon measurement efficiency of the PIC is 2-fold higher than the RAD7 detector and is far less influenced by moisture. We successfully deployed the system in 2.5 meters water depth over a 100 hours period in an anthropogenic influenced bay. Based on our high temporal resolution observations, the SGD flux was estimated to be 0-43.0 cm/d (mean: 25.4 ± 14.5 cm/d). The SGD fluxes pattern plotted together with the tidal variations revealed that tidal pumping may be the main force driving seawater recirculation into aquifers and thus affecting nutrient, carbon and other dissolved matters dynamics in coastal regions.
Physiology, metabolism, antibiotic resistance, and genetic diversity of Harveyi clade bacteria isolated from coastal mariculture system in China in the last two decades
Authors: Kang Hao , Yu Yongxiang , Liao Meijie , Wang Yingeng , Yang Guanpin , Zhang Zheng , Li Bin , Rong Xiaojun , Wang Chunyuan
Published: August 2022

Vibrio bacteria, particularly members of the Harveyi clade, are the most important pathogens of aquatic organisms that cause significant economic losses in the world. It is difficult to provide specific data on taxa of the Harveyi clade for biological research and prevention strategies. Therefore, we conducted an extensive phenotypic and antibiotic resistance study, as well as phylogenetic and molecular typing of 192 isolates of the Harveyi clade collection from 2000 to 2020 with a typical interannual difference from a coastal area in China. The isolates had a significant interspecific genetic and antibiotic resistance diversity. Based on the multilocus sequence analysis (MLSA) of housekeeping genes (gyrB, pyrH, recA, and atpA), 192 Harveyi clade isolates were rapidly and accurately classified into 10 species. The population of these isolates was composed of 95 sequence types (STs), of which 92 STs were newly identified, indicating a high degree of genetic diversity. ST327 ranked first, accounting for 11.5% of the total number of isolates (22 out of 192), followed by ST215 with 6.25%, while 63 STs included single isolates. At the metabolic level, the physiological and biochemical experiments revealed that all the Harveyi clade isolates were positive for oxidase and negative for melibiose. The isolates showed a varied tolerance to 11 antibiotics. No isolates were resistant to neomycin. The percentages of sulfadimidine-resistant strains (61 out of 192), sulfadiazine (44 out of 192), sulfamonomethoxine (44 out of 192), sulfamethoxazole (33 out of 192), thiamphenicol (34 out of 192), ciprofloxacin (52 out of 192), and enrofloxacin (31 out of 192) were 31.77%, 22.92%, 22.92%, 17.19%, 17.71%, 27.08%, and 16.15%, respectively. A proportion of 61.8% of the isolates presented a multiple antibiotic resistance index (MARI) lower than 0.1, indicating that the risk of antibiotic resistance transmission of most of the Harveyi clade is low in mariculture systems in China. These results provide substantial data to support further studies on the identification and genetic and metabolic diversity of Harveyi clade isolates in mariculture systems in China.
Resources and population traits modulate the association patterns in the common bottlenose dolphin living nearby the Tiber River estuary (Mediterranean Sea)
Authors: Pace Daniela Silvia , Ferri Sara , Giacomini Giancarlo , Di Marco Chiara , Papale Elena , Silvestri Margherita , Pedrazzi Giulia , Ventura Daniele , Casoli Edoardo , Ardizzone Giandomenico
Published: August 2022

Sociality and ecological drivers that can influence individual association patterns are infrequently considered in wildlife management, although they are essential aspects affecting animals’ responses to both human-related pressures and conservation strategies. In common bottlenose dolphins (Tursiops truncatus), sex-specific social dynamics and interactions with anthropogenic activities may affect grouping and induce changes in relationships between individuals. Out of a total of 347 individuals, we assessed the level of association among 68 bottlenose dolphins that have been sighted more than five times near the Roman coast (central Mediterranean Sea, Italy). The half-weight index (HWI) of dyadic associations, their network relations, and stability over time were investigated by using the SOCPROG software. Outcomes showed that females were more strongly associated than other individuals, with both preferred constant short-term associations and random long-term associations, possibly resulting in greater success in rearing young. Individuals interacting with the bottom trawl fishery showed weaker and short-term associations. Temporary disruption of individual associations during interaction with fishery and the relatively low number of females with calves participating in depredation seem to denote both the opportunistic nature of interactions with fishing vessels and the offspring-related protection strategy. The results show that the dolphins in this region maintain a complex but flexible social structure that varies with local biological requirements and is resilient to anthropogenic pressures.
Coastal carbonate system variability along an active lava–seawater interface
Authors: González-Santana David , Santana-Casiano Juana Magdalena , González Aridane G. , González-Dávila Melchor
Published: August 2022

Lava flows from the 2021 volcanic eruption in La Palma, Canary Islands, reached the shoreline during three events on September 28th, November 10th, and November 22nd, strongly affecting the seawater properties as they interacted with the seawater. The evolution of surface and water column physicochemical properties (temperature, salinity, carbonate system variables, and dissolved oxygen) was characterized during 13 visits to the frontal zone of the newly formed deltas. A large volume of hot (50°C measured on November 12th) and high salinity seawater promoted pH values in the frontal zone of 7.0 with important decreases in alkalinity, ΔAT, and total dissolved inorganic carbon, ΔCT, that reached 566 and 272 µmol kg−1, respectively. The addition of acids generated during the lava–seawater interaction (44.4 mmol), together with those used in the titration of carbonate alkalinity (796 ± 72 mmol) plus acids used in metal dissolution (21 mmol), was estimated with an average added proton concentration of 0.31 µmol kg−1 of seawater in the affected 2.7 · 106 m3 for November 12th. During this event, the decrease in pH and the increase in temperature increased the partial pressure of CO2, outgassing 2 tons of CO2, 40 times the daily emitted CO2 for this area under non-eruptive conditions. One month after the eruption, the studied physicochemical properties of the seawater close to the new deltas returned to the usual non-eruptive normal values, which include the presence of low salinity, low pH, and high CO2 gas diffusive emissions through submarine groundwater discharges observed between the formed deltas. The new mineral-rich deltas and the increase in solubility due to the low pH conditions contributed to the recovery of the affected area.
Theoretical progress of groundwater chemical evolution based on Tóthian theory: A review
Authors: Dong Hongzhi , Gao Zongjun
Published: August 2022

Tóthian theory refers to the gravity driven groundwater flow system (GFS) theory represented by Tóth, which mainly expounds the driving and distribution law of groundwater. The establishment and development of this theory not only deepened people’s understanding of the driving and distribution law of groundwater, but also greatly promoted the study of groundwater chemical evolution (GCE). Modern GCE research is mostly based on Tóthian theory, characterized by combining with advanced scientific and technological means. Based on the clue of time, this paper is divided into two parts. The first part mainly summarizes the establishment and development of Tóthian theory, including the exploration of groundwater driving force and distribution form by hydrogeologists before Tóthian theory, and the enrichment, development and application of Tóthian theory by geologists after its establishment. The second part mainly combs the main theories and application progress of GCE mechanism research, including the main theories and findings of GCE research before the emergence of Tóthian theory, as well as the research progresses of GCE after the emergence of Tóthian theory. With the flow of groundwater in GFS, groundwater undergoes continuous chemical evolution, which eventually leads to the transformation of hydrochemical types and the gradual increase of total dissolved solids (TDS). The distribution of GFS and GCE complement each other. The distribution of GFS directly determines the model of GCE, and the results of GCE also play a certain role in the distribution of GFS. GCE mainly includes dissolution, precipitation, cation exchange and adsorption, which is affected by the physical and chemical conditions of permeable media, organic matter content and microorganisms. GCE has the characteristics of universality, sustainability and diversity. With the increasing global population and the progresses of science and technology, the impact of human life, industrial and agricultural production on groundwater is deepening. The aggravation of pollution directly changes the chemical compositions of groundwater, resulting in changes of the law of GCE.
Eutrophication decreases Halophila beccarii plant organic carbon contribution to sequestration potential
Authors: Luo Hongxue , Liu Songlin , Ren Yuzheng , Jiang Zhijian , Wu Yunchao , Zhang Xia , Li Jinlong , Huang Xiaoping
Published: August 2022

Seagrass ecosystems rank among the most effective blue carbon sinks in climate change mitigation and greenhouse gas removal. Nutrient pollution has emerged as a leading threat to seagrass decline and has diminished the carbon sequestration potential in recent decades. Changes in the nutrient regime can also impact the organic carbon compositions (labile and refractory organic carbon compositions) of seagrass tissues, with important implications for determining the quantity and quality of carbon sequestration. However, there is still little information about the impact of nutrient loading on seagrass plant refractory organic carbon composition (ROC), which hinders our ability to reveal the driving mechanisms of anthropogenic factors that decrease seagrass organic carbon sequestration capability. Here, a multidisciplinary approach was employed to investigate the organic carbon variations of Halophila beccarii at five seagrass meadows with contrasting nutrient loading levels. The results showed that H. beccarii plant nitrogen (N) content ranged from 2.21% to 5.65%, which well reflected the external nutrient loading levels. High nutrient loading elevated labile organic carbon content, like free amino acids and soluble sugars. Nevertheless, ROC content (cellulose-associated organic matter) decreased with increasing nutrient loading, which presented a significant negative linear correlation with plant N content. These results provide evidence that eutrophic conditions enhance H. beccarii plant quality (high N and labile organic carbon) and consequently decrease plant ROC sequestration potential. This suggests that reducing nitrogen input to seagrass meadows would aid in increasing seagrass carbon storage.
Quick butt welding of steel sheets using the high-speed laser cladding method
Authors: Li Yongjian , Liu Xiaoting , Yan Shixing , He Peng
Published: August 2022

Laser butt welding of thin steel sheets without filler material was widely used in many industrial fields. However, it was very difficult to focus the small laser spot on the narrow gap between the sheets during the laser butt welding process. In this study, a new method to weld thin steel sheets using a high-speed laser cladding technique is proposed. Stainless steel sheets with a thickness of 0.5 mm were welded using the high-speed laser cladding process. The results illustrated that good weld joints could be obtained without obvious cracks and pores in most of the specimens. The joints were well formed even if the sheets were not spliced together entirely. The average tensile strength of the specimens was about 500 MPa, which is almost the same as that of the substrate. The results also showed that most of the failures did not happen in the welding region, which could be concluded that the strength of joints was higher than that of the substrate. The microstructure was determined using an optical microscope (OM) and scanning electron microscope (SEM). The results showed that it may be a good choice to use the high-speed laser cladding technique for butt welding of stainless steel sheets.
Effects of growth trajectory of shock index within 24 h on the prognosis of patients with sepsis
Authors: Xu Fengshuo , Zhang Luming , Huang Tao , Han Didi , Yang Rui , Zheng Shuai , Feng Aozi , Huang Liying , Yin Haiyan , Lyu Jun
Published: August 2022

Background

Sepsis is a serious disease with high clinical morbidity and mortality. Despite the tremendous advances in medicine and nursing, treatment of sepsis remains a huge challenge. Our purpose was to explore the effects of shock index (SI) trajectory changes on the prognosis of patients within 24 h after the diagnosis of sepsis.

Methods

This study was based on Medical Information Mart for Intensive Care IV (MIMIC- IV). The effects of SI on the prognosis of patients with sepsis were investigated using C-index and restricted cubic spline (RCS). The trajectory of SI in 24 h after sepsis diagnosis was classified by latent growth mixture modeling (LGMM). Cox proportional hazard model, double robust analysis, and subgroup analysis were conducted to investigate the influence of SI trajectory on in-hospital death and secondary outcomes.

Results

A total of 19,869 patients were eventually enrolled in this study. C-index showed that SI had a prognostic value independent of Sequential Organ Failure Assessment for patients with sepsis. Moreover, the results of RCS showed that SI was a prognostic risk factor. LGMM divided SI trajectory into seven classes, and patients with sepsis in different classes had notable differences in prognosis. Compared with the SI continuously at a low level of 0.6, the SI continued to be at a level higher than 1.0, and the patients in the class whose initial SI was at a high level of 1.2 and then declined had a worse prognosis. Furthermore, the trajectory of SI had a higher prognostic value than the initial SI.

Conclusion

Both initial SI and trajectory of SI were found to be independent factors that affect the prognosis of patients with sepsis. Therefore, in clinical treatment, we should closely monitor the basic vital signs of patients and arrive at appropriate clinical decisions on basis of their change trajectory.
Group-based trajectory analysis of acute pain after spine surgery and risk factors for rebound pain
Authors: Li Yi-Shiuan , Chang Kuang-Yi , Lin Shih-Pin , Chang Ming-Chau , Chang Wen-Kuei
Published: August 2022

Background

This retrospective study was designed to explore the types of postoperative pain trajectories and their associated factors after spine surgery.

Materials and methods

This study was conducted in a single medical center, and patients undergoing spine surgery with intravenous patient-controlled analgesia (IVPCA) for postoperative pain control between 2016 and 2018 were included in the analysis. Maximal pain scores were recorded daily in the first postoperative week, and group-based trajectory analysis was used to classify the variations in pain intensity over time and investigate predictors of rebound pain after the end of IVPCA. The relationships between the postoperative pain trajectories and the amount of morphine consumption or length of hospital stay (LOS) after surgery were also evaluated.

Results

A total of 3761 pain scores among 547 patients were included in the analyses and two major patterns of postoperative pain trajectories were identified: Group 1 with mild pain trajectory (87.39%) and Group 2 with rebound pain trajectory (12.61%). The identified risk factors of the rebound pain trajectory were age less than 65 years (odds ratio [OR]: 1.89; 95% CI: 1.12–3.20), female sex (OR: 2.28; 95% CI: 1.24–4.19), and moderate to severe pain noted immediately after surgery (OR: 3.44; 95% CI: 1.65–7.15). Group 2 also tended to have more morphine consumption (p < 0.001) and a longer length of hospital stay (p < 0.001) than Group 1.

Conclusion

The group-based trajectory analysis of postoperative pain provides insight into the patterns of pain resolution and helps to identify unusual courses. More aggressive pain management should be considered in patients with a higher risk for rebound pain after the end of IVPCA for spine surgery.
ReDisX, a machine learning approach, rationalizes rheumatoid arthritis and coronary artery disease patients uniquely upon identifying subpopulation differentiation markers from their genomic data
Authors: Yip Hiu F. , Chowdhury Debajyoti , Wang Kexin , Liu Yujie , Gao Yao , Lan Liang , Zheng Chaochao , Guan Daogang , Lam Kei F. , Zhu Hailong , Tai Xuecheng , Lu Aiping
Published: August 2022

Diseases originate at the molecular-genetic layer, manifest through altered biochemical homeostasis, and develop symptoms later. Hence, symptomatic diagnosis is inadequate to explain the underlying molecular-genetic abnormality and individual genomic disparities. The current trends include molecular-genetic information relying on algorithms to recognize the disease subtypes through gene expressions. Despite their disposition toward disease-specific heterogeneity and cross-disease homogeneity, a gap still exists in describing the extent of homogeneity within the heterogeneous subpopulation of different diseases. They are limited to obtaining the holistic sense of the whole genome-based diagnosis resulting in inaccurate diagnosis and subsequent management. Addressing those ambiguities, our proposed framework, ReDisX, introduces a unique classification system for the patients based on their genomic signatures. In this study, it is a scalable machine learning algorithm deployed to re-categorize the patients with rheumatoid arthritis and coronary artery disease. It reveals heterogeneous subpopulations within a disease and homogenous subpopulations across different diseases. Besides, it identifies granzyme B (GZMB) as a subpopulation-differentiation marker that plausibly serves as a prominent indicator for GZMB-targeted drug repurposing. The ReDisX framework offers a novel strategy to redefine disease diagnosis through characterizing personalized genomic signatures. It may rejuvenate the landscape of precision and personalized diagnosis and a clue to drug repurposing.
Immunomodulatory effects of new phytotherapy on human macrophages and TLR4- and TLR7/8-mediated viral-like inflammation in mice
Authors: Schapovalova Olesia , Gorlova Anna , de Munter Johannes , Sheveleva Elisaveta , Eropkin Mikhail , Gorbunov Nikita , Sicker Michail , Umriukhin Aleksei , Lyubchyk Sergiy , Lesch Klaus-Peter , Strekalova Tatyana , Schroeter Careen A.
Published: August 2022

Background

While all efforts have been undertaken to propagate the vaccination and develop remedies against SARS-CoV-2, no satisfactory management of this infection is available yet. Moreover, poor availability of any preventive and treatment measures of SARS-CoV-2 in economically disadvantageous communities aggravates the course of the pandemic. Here, we studied a new immunomodulatory phytotherapy (IP), an extract of blackberry, chamomile, garlic, cloves, and elderberry as a potential low-cost solution for these problems given the reported efficacy of herbal medicine during the previous SARS virus outbreak.

Methods

The key feature of SARS-CoV-2 infection, excessive inflammation, was studied in in vitro and in vivo assays under the application of the IP. First, changes in tumor-necrosis factor (TNF) and lnteurleukin-1 beta (IL-1β) concentrations were measured in a culture of human macrophages following the lipopolysaccharide (LPS) challenge and treatment with IP or prednisolone. Second, chronically IP-pre-treated CD-1 mice received an agonist of Toll-like receptors (TLR)-7/8 resiquimod and were examined for lung and spleen expression of pro-inflammatory cytokines and blood formula. Finally, chronically IP-pre-treated mice challenged with LPS injection were studied for “sickness” behavior. Additionally, the IP was analyzed using high-potency-liquid chromatography (HPLC)-high-resolution-mass-spectrometry (HRMS).

Results

LPS-induced in vitro release of TNF and IL-1β was reduced by both treatments. The IP-treated mice displayed blunted over-expression of SAA-2, ACE-2, CXCL1, and CXCL10 and decreased changes in blood formula in response to an injection with resiquimod. The IP-treated mice injected with LPS showed normalized locomotion, anxiety, and exploration behaviors but not abnormal forced swimming. Isoquercitrin, choline, leucine, chlorogenic acid, and other constituents were identified by HPLC-HRMS and likely underlie the IP immunomodulatory effects.

Conclusions

Herbal IP-therapy decreases inflammation and, partly, “sickness behavior,” suggesting its potency to combat SARS-CoV-2 infection first of all via its preventive effects.
Clostridioides difficile infection epidemiology and clinical characteristics in COVID-19 pandemic
Authors: Vázquez-Cuesta Silvia , Olmedo María , Reigadas Elena , Alcalá Luis , Marín Mercedes , Muñoz Patricia , Bouza Emilio
Published: August 2022

Information on Clostridioides difficile infection (CDI) in patients with COVID-19 is scarce and points to an overall decrease of episodes during the pandemic. This situation results paradoxical, as COVID-19 patients had long periods of hospital stay and high use of antibiotics. We conducted a retrospective study from January 1st 2019 to December 31st 2020 comparing the incidence of hospital-acquired episodes of CDI (HA-CDI) among patients with and without COVID-19 admitted to our institution. During the study period, there were 47,048 patient admissions in 2019, 35,662 admissions of patients without COVID-19 in 2020 and 6,763 of COVID-19 patients. There were 68 episodes of HA-CDI in COVID-19 patients (14.75/10,000 days), 159 in 2020-non-COVID-19 patients (5.54/10,000 days) and 238 in 2019 (6.80/10,000 days). Comparison of HA-CDI in COVID-19 and non-COVID-19 patients indicates it occurs more frequently, in terms of CDI disease severity, COVID-19 does not seem to have a negative impact.
The effect of targeted hyperoxemia in a randomized controlled trial employing a long-term resuscitated, model of combined acute subdural hematoma and hemorrhagic shock in swine with coronary artery disease: An exploratory, hypothesis-generating study
Authors: Datzmann Thomas , Messerer David Alexander Christian , Münz Franziska , Hoffmann Andrea , Gröger Michael , Mathieu René , Mayer Simon , Gässler Holger , Zink Fabian , McCook Oscar , Merz Tamara , Scheuerle Angelika , Wolfschmitt Eva-Maria , Thebrath Timo , Zuech Stefan , Calzia Enrico , Asfar Pierre , Radermacher Peter , Kapapa Thomas
Published: August 2022

Controversial evidence is available regarding suitable targets for the arterial O2 tension (PaO2) after traumatic brain injury and/or hemorrhagic shock (HS). We previously demonstrated that hyperoxia during resuscitation from hemorrhagic shock attenuated cardiac injury and renal dysfunction in swine with coronary artery disease. Therefore, this study investigated the impact of targeted hyperoxemia in a long-term, resuscitated model of combined acute subdural hematoma (ASDH)-induced brain injury and HS. The prospective randomized, controlled, resuscitated animal investigation consisted of 15 adult pigs. Combined ASDH plus HS was induced by injection of 0.1 ml/kg autologous blood into the subdural space followed by controlled passive removal of blood. Two hours later, resuscitation was initiated comprising re-transfusion of shed blood, fluids, continuous i.v. noradrenaline, and either hyperoxemia (target PaO2 200 – 250 mmHg) or normoxemia (target PaO2 80 – 120 mmHg) during the first 24 h of the total of 54 h of intensive care. Systemic hemodynamics, intracranial and cerebral perfusion pressures, parameters of brain microdialysis and blood biomarkers of brain injury did not significantly differ between the two groups. According to the experimental protocol, PaO2 was significantly higher in the hyperoxemia group at the end of the intervention period, i.e., at 24 h of resuscitation, which coincided with a higher brain tissue PO2. The latter persisted until the end of observation period. While neurological function as assessed using the veterinary Modified Glasgow Coma Score progressively deteriorated in the control group, it remained unaffected in the hyperoxemia animals, however, without significant intergroup difference. Survival times did not significantly differ in the hyperoxemia and control groups either. Despite being associated with higher brain tissue PO2 levels, which were sustained beyond the intervention period, targeted hyperoxemia exerted neither significantly beneficial nor deleterious effects after combined ASDH and HS in swine with pre-existing coronary artery disease. The unavailability of a power calculation and, thus, the limited number of animals included, are the limitations of the study.
Post-traumatic knee osteoarthritis; the role of inflammation and hemarthrosis on disease progression
Authors: Evers Bob J. , Van Den Bosch Martijn H. J. , Blom Arjen B. , van der Kraan Peter M. , Koëter Sander , Thurlings Rogier M.
Published: August 2022

Knee injuries such as anterior cruciate ligament ruptures and meniscal injury are common and are most frequently sustained by young and active individuals. Knee injuries will lead to post-traumatic osteoarthritis (PTOA) in 25–50% of patients. Mechanical processes where historically believed to cause cartilage breakdown in PTOA patients. But there is increasing evidence suggesting a key role for inflammation in PTOA development. Inflammation in PTOA might be aggravated by hemarthrosis which frequently occurs in injured knees. Whereas mechanical symptoms (joint instability and locking of the knee) can be successfully treated by surgery, there still is an unmet need for anti-inflammatory therapies that prevent PTOA progression. In order to develop anti-inflammatory therapies for PTOA, more knowledge about the exact pathophysiological mechanisms and exact course of post-traumatic inflammation is needed to determine possible targets and timing of future therapies.
Imaging and biopsy of HIV-infected individuals undergoing analytic treatment interruption
Authors: Lau Chuen-Yen , Adan Matthew A. , Earhart Jessica , Seamon Cassie , Nguyen Thuy , Savramis Ariana , Adams Lindsey , Zipparo Mary-Elizabeth , Madeen Erin , Huik Kristi , Grossman Zehava , Chimukangara Benjamin , Wulan Wahyu Nawang , Millo Corina , Nath Avindra , Smith Bryan R. , Ortega-Villa Ana M. , Proschan Michael , Wood Bradford J. , Hammoud Dima A. , Maldarelli Frank
Published: August 2022

Background

HIV persistence during antiretroviral therapy (ART) is the principal obstacle to cure. Lymphoid tissue is a compartment for HIV, but mechanisms of persistence during ART and viral rebound when ART is interrupted are inadequately understood. Metabolic activity in lymphoid tissue of patients on long-term ART is relatively low, and increases when ART is stopped. Increases in metabolic activity can be detected by 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and may represent sites of HIV replication or immune activation in response to HIV replication.

Methods

FDG-PET imaging will be used to identify areas of high and low metabolic uptake in lymphoid tissue of individuals undergoing long-term ART. Baseline tissue samples will be collected. Participants will then be randomized 1:1 to continue or interrupt ART via analytic treatment interruption (ATI). Image-guided biopsy will be repeated 10 days after ATI initiation. After ART restart criteria are met, image-guided biopsy will be repeated once viral suppression is re-achieved. Participants who continued ART will have a second FDG-PET and biopsies 12–16 weeks after the first. Genetic characteristics of HIV populations in areas of high and low FDG uptake will be assesed. Optional assessments of non-lymphoid anatomic compartments may be performed to evaluate HIV populations in distinct anatomic compartments.

Anticipated results

We anticipate that PET standardized uptake values (SUV) will correlate with HIV viral RNA in biopsies of those regions and that lymph nodes with high SUV will have more viral RNA than those with low SUV within a patient. Individuals who undergo ATI are expected to have diverse viral populations upon viral rebound in lymphoid tissue. HIV populations in tissues may initially be phylogenetically diverse after ATI, with emergence of dominant viral species (clone) over time in plasma. Dominant viral species may represent the same HIV population seen before ATI.

Discussion

This study will allow us to explore utility of PET for identification of HIV infected cells and determine whether high FDG uptake respresents areas of HIV replication, immune activation or both. We will also characterize HIV infected cell populations in different anatomic locations. The protocol will represent a platform to investigate persistence and agents that may target HIV populations.

Study protocol registration

Identifier: NCT05419024.
Prevalence of antibiotic resistance genes in drinking and environmental water sources of the Kathmandu Valley, Nepal
Authors: Amarasiri Mohan , Takezawa Tsubasa , Malla Bikash , Furukawa Takashi , Sherchand Jeevan B. , Haramoto Eiji , Sei Kazunari
Published: August 2022

Antibiotic-resistant bacteria-associated infections are responsible for more than 1.2 million annual deaths worldwide. In low- and middle-income countries (LMICs), the consumption of antibiotics for human and veterinary uses is not regulated effectively. Overused and misused antibiotics can end up in aquatic environments, which may act as a conduit for antibiotic resistance dissemination. However, data on the prevalence of antibiotic resistance determinants in aquatic environments are still limited for LMICs. In this study, we evaluated the prevalence and concentration of antibiotic resistance genes (ARGs) in different drinking and environmental water sources collected from the Kathmandu Valley, Nepal, using droplet digital polymerase chain reaction to understand the current situation of ARG contamination. River water and shallow dug well water sources were the most contaminated with ARGs. Almost all samples containedsul1(94%), andintI1andtet(A) were detected in 83 and 60% of the samples, respectively. Maximum ARG concentration varied between 4.2 log10copies/100 ml formecAand 9.3 log10copies/100 ml forsul1. Significant positive correlations were found between ARGs (r> 0.5,p< 0.01), except formecA, qnrS, andvanA. Assul1andintI1were detected in almost all samples, the presence of these genes in a given sample may need to be considered as background antibiotic resistance in LMICs. Therefore, monitoring of ARGs, such as β-lactam ARGs, quinolone resistance genes, and vancomycin resistance genes, may provide a better picture of the antibiotic resistance determinants in aquatic environments of LMICs.
Antibacterial activity of novel linear polyamines against Staphylococcus aureus
Authors: Douglas Edward J. A. , Alkhzem Abdulaziz H. , Wonfor Toska , Li Shuxian , Woodman Timothy J. , Blagbrough Ian S. , Laabei Maisem
Published: August 2022

New therapeutic options are urgently required for the treatment of Staphylococcus aureus infections. Accordingly, we sought to exploit the vulnerability of S. aureus to naturally occurring polyamines. We have developed and tested the anti-staphylococcal activity of three novel linear polyamines based on spermine and norspermine. Using a panel of genetically distinct and clinically relevant multidrug resistant S. aureus isolates, including the polyamine resistant USA300 strain LAC, compound AHA-1394 showed a greater than 128-fold increase in inhibition against specific S. aureus strains compared to the most active natural polyamine. Furthermore, we show that AHA-1394 has superior biofilm prevention and biofilm dispersal properties compared to natural polyamines while maintaining minimal toxicity toward human HepG2 cells. We examined the potential of S. aureus to gain resistance to AHA-1394 following in vitro serial passage. Whole genome sequencing of two stable resistant mutants identified a gain of function mutation (S337L) in the phosphatidylglycerol lysyltransferase mprF gene. Inactivation of mutant mprF confirmed the importance of this allele to AHA-1394 resistance. Importantly, AHA-1394 resistant mutants showed a marked decrease in relative fitness and increased generation time. Intriguingly, mprF::S337L contributed to altered surface charge only in the USA300 background whereas increased cell wall thickness was observed in both USA300 and SH1000. Lastly, we show that AHA-1394 displays a particular proclivity for antibiotic potentiation, restoring sensitivity of MRSA and VRSA isolates to daptomycin, oxacillin and vancomycin. Together this study shows that polyamine derivatives are impressive drug candidates that warrant further investigation.
Microencapsulation and in situ incubation methodology for the cultivation of marine bacteria
Authors: Pope Emily , Cartmell Christopher , Haltli Bradley , Ahmadi Ali , Kerr Russell G.
Published: August 2022

Environmental microorganisms are important sources of biotechnology innovations; however, the discovery process is hampered by the inability to culture the overwhelming majority of microbes. To drive the discovery of new biotechnology products from previously unculturable microbes, several methods such as modification of media composition, incubation conditions, single-cell isolation, and in situ incubation, have been employed to improve microbial recovery from environmental samples. To improve microbial recovery, we examined the effect of microencapsulation followed by in situ incubation on the abundance, viability, and diversity of bacteria recovered from marine sediment. Bacteria from marine sediment samples were resuspended or encapsulated in agarose and half of each sample was directly plated on agar and the other half inserted into modified Slyde-A-Lyzer™ dialysis cassettes. The cassettes were incubated in their natural environment (in situ) for a week, after which they were retrieved, and the contents plated. Colony counts indicated that bacterial abundance increased during in situ incubation and that cell density was significantly higher in cassettes containing non-encapsulated sediment bacteria. Assessment of viability indicated that a higher proportion of cells in encapsulated samples were viable at the end of the incubation period, suggesting that agarose encapsulation promoted higher cell viability during in situ incubation. One hundred and 46 isolates were purified from the study (32–38 from each treatment) to assess the effect of the four treatments on cultivable bacterial diversity. In total, 58 operational taxonomic units (OTUs) were identified using a 99% 16S rRNA gene sequence identity threshold. The results indicated that encapsulation recovered greater bacterial diversity from the sediment than simple resuspension (41 vs. 31 OTUs, respectively). While the cultivable bacterial diversity decreased by 43%–48% after in situ incubation, difficult-to-culture (Verrucomicrobia) and obligate marine (Pseudoalteromonas) taxa were only recovered after in situ incubation. These results suggest that agarose encapsulation coupled with in situ incubation in commercially available, low-cost, diffusion chambers facilitates the cultivation and improved recovery of bacteria from marine sediments. This study provides another tool that microbiologists can use to access microbial dark matter for environmental, biotechnology bioprospecting.
Antimicrobial therapy in complicated rhinosinusitis
Authors: Beatrice Simion-Antonie Catrinel , Luiza Bejenaru Paula , Bogdan Popescu , Simona Berteșteanu Gloria , Mihnea Condeescu-Cojocărița , Ionela Cîrstea Anca , Elena Diaconu Teodora , Petra Taher Bianca , Simona-Andreea Rujan , Doinița Oașă Irina , Gabriel Berteșteanu Șerban Vifor , Raluca Grigore
Published: August 2022

Introduction

Complicated rhinosinusitis is a rare but life-threatening pathology that requires both medical and surgical treatment as soon as possible. The spread of the infection from the paranasal sinuses affects, most often, the orbit, patients presenting diplopia, preseptal cellulitis, orbital cellulitis, or even blindness alongside exteriorization of puss from the middle meatus and nasal obstruction.

Materials and methods

We carried out a retrospective review of 32 patients that were diagnosed in our clinic with complicated rhinosinusitis from 2015 to 2022. All the patients received at least one intravenous antibiotic, and some also received antifungal drugs. All patients underwent surgery, either endoscopically or combined approach. Nasal washout or nasal swabs during surgery were sent for laboratory examination in all patients, and we studied the microbial etiology in these extensive infections. A database with all the information regarding demographic and medical data was established.

Results

78% of the patients were male, with a mean age of 50.55. A wide range of antibiotics were used, while some patients, diagnosed with mucormycosis also received antifungal drugs. The mean hospitalization period was 12 days. We correlated the type of antibiotic with the hospitalization period and the outcome but also the degree of involvement of the orbit and the microbial strains identified.

Discussion

The management of patients with complicated rhinosinusitis is complex and dynamic and it must be tailored to every patient, after an interdisciplinary meeting with the infectious disease specialist, ophthalmologist, and rhinologist. The microbial strains that produce such important infections are sometimes multi-resistant or combined, patients usually already had followed a course of antibiotics at home, and choosing the right treatment is sometimes challenging.
Impairment of the Zn/Cd detoxification systems affects the ability of Salmonella to colonize Arabidopsis thaliana
Authors: Visconti Sabina , Astolfi Maria Luisa , Battistoni Andrea , Ammendola Serena
Published: August 2022

Salmonella capacity to colonize different environments depends on its ability to respond efficiently to fluctuations in micronutrient availability. Among micronutrients, Zn, besides playing an essential role in bacterial physiology, is a key element whose concentration can influence bacterial survival in a particular niche. Plant colonization by Salmonella enterica was described for several years, and some molecular determinants involved in this host-pathogen interaction have started to be characterized. However, it is still unclear if Zn plays a role in the outcome of this interaction, as well established for animal hosts that employ nutritional immunity strategies to counteract pathogens infections. In this study, we have investigated the involvement of Salmonella Typhimurium main effectors of zinc homeostasis in plant colonization, using Arabidopsis thaliana as a model host. The results show that to colonize plant tissues, Salmonella takes advantage of its ability to export excess metal through the efflux pumps ZntA and ZitB. In fact, the deletion of these Zn/Cd detoxification systems can affect bacterial persistence in the shoots, depending on metal availability in the plant tissues. The importance of Salmonella ability to export excess metal was enhanced in the colonization of plants grown in high Zn conditions. On the contrary, the bacterial disadvantage related to Zn detoxification impairment can be abrogated if the plant cannot efficiently translocate Zn to the shoots. Overall, our work highlights the role of Zn in Salmonella-plant interaction and suggests that modulation of plant metal content through biofortification may be an efficient strategy to control pathogen colonization.
The exceptionally efficient quorum quenching enzyme LrsL suppresses Pseudomonas aeruginosa biofilm production
Authors: Rehman Zahid Ur , Momin Afaque A. , Aldehaiman Abdullah , Irum Tayyaba , Grünberg Raik , Arold Stefan T.
Published: August 2022

Quorum quenching (QQ) is the enzymatic degradation of molecules used by bacteria for synchronizing their behavior within communities. QQ has attracted wide attention due to its potential to inhibit biofilm formation and suppress the production of virulence factors. Through its capacity to limit biofouling and infections, QQ has applications in water treatment, aquaculture, and healthcare. Several different QQ enzymes have been described; however, they often lack the high stability and catalytic efficiency required for industrial applications. Previously, we identified genes from genome sequences of Red Sea sediment bacteria encoding potential QQ enzymes. In this study, we report that one of them, named LrsL, is a metallo-β-lactamase superfamily QQ enzyme with outstanding catalytic features. X-ray crystallography shows that LrsL is a zinc-binding dimer. LrsL has an unusually hydrophobic substrate binding pocket that can accommodate a broad range of acyl-homoserine lactones (AHLs) with exceptionally high affinity. In vitro, LrsL achieves the highest catalytic efficiency reported thus far for any QQ enzyme with a Kcat/KM of 3 × 107. LrsL effectively inhibited Pseudomonas aeruginosa biofilm formation without affecting bacterial growth. Furthermore, LrsL suppressed the production of exopolysaccharides required for biofilm production. These features, and its capacity to regain its function after prolonged heat denaturation, identify LrsL as a robust and unusually efficient QQ enzyme for clinical and industrial applications.