bluuebunny/crossref_metadata_2025 huggingface dataset:
Alteration of Bile Acids and Omega-6 PUFAs Are Correlated With the Progression and Prognosis of Drug-Induced Liver Injury
Authors: Zhao Shuang , Fu Haoshuang , Zhou Tianhui , Cai Minghao , Huang Yan , Gan Qinyi , Zhang Chenxi , Qian Cong , Wang Jiexiao , Zhang Zhenglan , Wang Xiaolin , Xiang Xiaogang , Xie Qing
Published: April 2022

Background & Aims

Drug-induced liver injury (DILI) is one of the leading causes of liver failure with some of the patients progressed to chronic DILI. The mechanisms underlying the severity and chronicity of DILI are poorly elucidated and the biomarkers are limited. Metabolites and gut microbiota played a crucial role in the development of various liver diseases. Herein, a systematic analysis of serum metabolites and gut microbiota was performed in DILI patients, aiming to identify metabolites correlated with the progression and clinical prognosis of DILI.

Methods

Various serum metabolites were quantitated using a metabolite array technology in this prospective study. Gut microbiome compositions and the expression profiles of liver genes were determined in patients with DILI and healthy controls.

Results

Metabolomic analysis revealed that bile acids (BAs) and polyunsaturated fatty acids (PUFAs) were closely related to DILI severity and chronicity respectively. The ratios of serum primary/secondary BAs and omega-6/omega-3 PUFAs were elevated in DILI patients. A model established by adrenic acid (AdA) and aspartic acid (Asp) exerts good performance for predicting the chronicity of DLIL. Hepatic transcriptome revealed enhanced expression of PUFA peroxidation and supressed expression of BA synthesis related genes in DILI patients. In addition, Lactic acid bacteria and BA converting bacteria were increased in gut of DILI patients. Besides, elevated serum malondialdehyde (MDA) and fibroblast growth factor 19 (FGF19) was observed in DILI patients.

Conclusion

BAs and PUFAs could be potent markers for the severity and chronicity of DILI respectively. The panel of AdA and Asp could be ideal predictive model for the risk of chronicity at the acute stage of DILI. Gut microbiota might act as a negative feedback mechanism to maintain the homeostasis of BAs and PUFAs via FGF19 signalling and PUFA saturation, respectively. Our study revealed novel biomarkers for severe and chronic DILI and provided new therapeutic targets for DILI.
The Antioxidant, Anti-Inflammatory and Immunomodulatory Effects of Camel Milk
Authors: Behrouz Sepide , Saadat Saeideh , Memarzia Arghavan , Sarir Hadi , Folkerts Gert , Boskabady Mohammad Hossein
Published: April 2022

Camel milk (CM) has been found to have several health benefits, including antiviral, antibacterial, anti-tumor, anti-fungal, antioxidant, hypoglycaemic and anti-cancer activities. In addition, CM can counter signs of aging and may be a useful naturopathic treatment for autoimmune diseases. The composition of CM varies with geographic origin, feeding conditions, seasonal and physiological changes, genetics and camel health status. In the present review, we collate the diverse scientific literature studying antioxidant, anti-inflammatory and immunomodulatory effects of CM and its bioactive compounds. The databases Scopus, PubMed, and Web of Science were searched until the end of September 2021 using the keywords: camel milk, antioxidant, anti-inflammatory, immunomodulatory. The anti-inflammatory mechanism of CM in various inflammatory disorders was consistently reported to be through modulating inflammatory cells and mediators. The common anti-inflammatory bioactive components of CM seem to be lactoferrin. The antioxidant effects of α-lactalbumin, β-caseins and vitamin C of CM work by reducing or inhibiting the production of reactive oxygen species (ROS), hydroxyl radicals, nitric oxide (NO), superoxide anions and peroxyl radicals, likely alleviating oxidative stress. Higher levels of protective proteins such as lysozyme, IgG and secretory IgA compared to cow’s milk, and insulin-like protein activity of CM on ß cells appear to be responsible for the immunomodulatory properties of CM. The evidence indicates that CM and its bioactive components has the potential to be a therapeutic value for diseases that are caused by inflammation, oxidative stress and/or immune-dysregulation.
Case Report: Pemphigoid Nodularis—Five Patients With Many Years of Follow-Up and Review of the Literature
Authors: Szymanski Konrad , Adaszewska Alicja , Jakubowska Beata , Kowalewski Cezary , Pietrzyk Ewelina , Wozniak Katarzyna
Published: April 2022

Pemphigoid nodularis is a rare form of pemphigoid that joins the clinical picture of prurigo nodularis and the immunological features of bullous pemphigoid, which is therapeutically challenging. Here, we analyze five female patients with a long-lasting course of nodular pemphigoid in terms of clinical and immunological characteristics and therapy. All the patients fulfilled clinical and immunological criteria of nodular pemphigoid. We applied numerous techniques allowing the proper diagnosis: direct and indirect immunofluorescence, salt split skin, ELISA, BIOCHIP, and fluorescence overlay antigen mapping using laser scanning confocal microscopy. Our study showed that 4 of 5 patients fulfilled the clinical and immunological criteria of nodular bullous pemphigoid. Two out of 4 patients presented exclusively nodular lesions; in the other two patients, blisters and erythematous lesions preceded prurigo-like lesions by a few years. The remaining patient had clinical and immunological criteria of nodular mucous membrane pemphigoid, presenting oral erosions, scarring conjunctivitis, and numerous disseminated nodules on the skin. All the patients were treated with multiple medicines; however, it was observed that the use of clobetasol propionate on the entire body plus antidepressants best controlled the disease. Pemphigoid nodularis mainly occurs in elderly women. In cases with coexisting psychological problems, antidepressants should be considered as an important complementary therapy to the basic one with clobetasol propionate.
First Isolation and Characterization of Streptococcus agalactiae From a Stranded Wild Common Dolphin (Delphinus delphis)
Authors: Morick Danny , Davidovich Nadav , Zemah-Shamir Ziv , Bigal Eyal , Rokney Assaf , Ron Merav , Blum Shlomo E. , Fleker Marcelo , Soto Esteban , Heckman Taylor I. , Lau Stanley C. K. , Wosnick Natascha , Tchernov Dan , Scheinin Aviad P.
Published: April 2022

Streptococcosis is an infectious bacterial disease of both homeotherms and poikilotherms. Among the Streptococcus species that infect marine animals, Streptococcus agalactiae has the broadest host spectrum, including different aquatic organisms in freshwater and marine environments. The common dolphin (Delphinus delphis) is categorized as Endangered in the Mediterranean Sea. There are few reports of a streptococcal infection of D. delphis, caused by Streptococcus phocae and Streptococcus iniae. Here we report the isolation and identification of S. agalactiae in a stranded, wild male common dolphin that was found dead in September 2020 on the seashore next to the city of Bat-Yam, Israel. The carcass was fresh with a moderate nutritional status and with no apparent fishing gear or other anthropogenic-related signs. A post-mortem examination did not reveal an apparent cause of death, but further laboratory analysis demonstrated a S. agalactiae bacterial presence in urine, lungs and pericardial fluid that was characterized as type Ia-ST7 by whole genome sequencing. Interestingly, this isolate was found to be almost identical to another isolate recently recovered from a wild sandbar shark (Carcharhinus plumbeus) in the same area in Israel, the eastern Mediterranean Sea.
Highly Productive Ice Algal Mats in Arctic Melt Ponds: Primary Production and Carbon Turnover
Authors: Hancke Kasper , Kristiansen Svein , Lund-Hansen Lars Chresten
Published: April 2022

Arctic summer sea ice extent is decreasing and thinning, forming melt ponds that cover more than 50% of the sea ice area during the peak of the melting season. Despite of this, ice algal communities in melt ponds are understudied and so are their contribution to the Arctic Ocean primary production and carbon turnover. While melt ponds have been considered as low productive, recent studies suggest that accumulated ice algal potentially facilitate high and yet overlooked rates of carbon turnover. Here we report on ice algal communities forming dense mats not previously described, collected from melt ponds in the northern Barents Sea in July. We document on distinct layered and brown colored mats with high carbon assimilation and net primary production rates compared to ice algal communities and aggregates, in fact comparable to benthic microalgae at temperate tidal flats. Rates of gross and net primary production, as well as community respiration rates were obtained from oxygen micro profiling, and carbon assimilation calculations were supported by 14C incubations, pigment analysis and light microscopy examinations. The melt pond algal mats consisted of distinct colored layers and differed from aggregates with a consisted layered structure. We accordingly propose the term melt pond algal mats, and further speculate that these dense ice algal mats may provide an important yet overlooked source of organic carbon in the Arctic food-web. A foodweb component likely very sensitive to climate driven changes in the Arctic Ocean and pan-Arctic seas.
Modification of Asphalt Modified by Packaging Waste EVA and Graphene Oxide
Authors: Zhang Maorong , Lian Chao , Wang Junyuan , Wang Hongfu , Cheng Bo
Published: April 2022

A composite modifier made from waste ethylene-vinyl acetate copolymer (WEVA) and graphene oxide (GO) is used to modify asphalt used to pave the roadway. At the same time, the effect of GO on the related properties of modified composite asphalt is investigated in terms of softening point, penetration, ductility, as well as distribution. The preparation of the composite modifier can reduce the modification’s complexity and enhance the modifier’s dispersion in the asphalt system in the storage phase. By increasing WEVA and GO contents, the softening point of modified composite asphalt increases, and both the penetration and ductility decrease. It is proved that the high-temperature performance of composite asphalt modified by WEVA and GO is better than that of modified asphalt with WEVA. The distribution characteristics of modified asphalt on a fluorescence microscope show that by adding more GO, we get a more even and smaller “bee structure” asphalt system. It indicates that GO can promote dispersion and stop the aggregation of WEVA. The FTIR spectrum results show that the composite modification by adding WEVA and GO is a physical modification, indicating GO can physically prevent the aggregation of the polymers in the storage phase. We present a schematic of the effect on GO and WEVA in asphalt modification to show the improvement in the distribution of the asphalt system from GO. In all, this study provides an idea for the preparation of modified composite asphalt and the application of nano-materials.
A Brief Overview of Bioinspired Robust Hydrogel Based Shape Morphing Functional Structure for Biomedical Soft Robotics
Authors: Goyal Rohit , Mitra Santanu
Published: April 2022

Biomimetic and soft robotics research has been inspired by many biological organisms focusing on soft structural composites reinforced by stiff constituents. In the case of synthetic soft structural materials, hydrogels are very similar to the biological soft tissues/organs, owing to their “wet and soft” properties, their elastic performance, biodegradability, and biocompatibility. However, the current scope of hydrogel applications is usually hampered by their feeble mechanical properties. Although significant progress has been made in developing intense, challenging, and stretchable hydrogels, it is still challenging to realize the optimal magnitude of physical and mechanical properties altogether in synthetic hydrogels. This review briefly focuses on the hydrogel fibrous shape-morphing composite structure and its functionalities. The nature-inspired, fiber-reinforced soft hydrogel shape-morphing functional composite structure delivers them a cartilage-like anisotropic behavior. They could have broad potential applications in various areas, including tissue engineering, soft robotics, stretchable and bio-integrated electronics, microfluidics, and biomedical devices.
Biogeographic, Driving Factors, Assembly, and Co-occurrence Patterns of Archaeal Community in Biocrusts
Authors: Li Yuanlong , Wei Jingyi , Yang Haijian , Zhang Delu , Hu Chunxiang
Published: April 2022

Archaea exhibit strong community heterogeneity with microhabitat gradients and are a non-negligible part of biocrust’s microorganisms. The study on archaeal biogeography in biocrusts could provide new insights for its application in environmental restoration. However, only a few studies on assembly processes and co-occurrence patterns of the archaeal community in patchy biocrusts have been reported, especially considering the number of species pools (SPs). Here, we comprehensively collected biocrusts across 3,500 km of northern China. Different successional biocrusts from various regions contain information of local climate and microenvironments, which can shape multiple unique archaeal SPs. The archaeal community differences in the same successional stage exceeded the variations between successional stages, which was due to the fact that the heterogeneous taxa tended to exchange between unknown patches driven by drift. We also comparatively studied the driving forces of community heterogeneity across three to ten SPs, and assembly and co-occurrence patterns were systematically analyzed. The results revealed that the impact of spatial factors on biogeographic patterns was greater than that of environmental and successional factors and that impact decreased with the number of SPs considered. Meanwhile, community heterogeneity at the phylogenetic facet was more sensitive to these driving factors than the taxonomic facet. Subgroups 1 (SG1) and 2 (SG2) of the archaeal communities in biocrusts were dominated by Nitrososphaeraceae and Haloarchaea, respectively. The former distribution pattern was associated with non-salinity-related variables and primarily assembled by drift, whereas the latter was associated with salinity-related variables and primarily assembled by homogeneous selection. Finally, network analysis indicated that the SG1 network had a higher proportion of competition and key taxa than the SG2 network, but the network of SG2 was more complex. Our study suggested that the development of the archaeal community was not consistent with biocrusts succession. The dominant taxa may determine the patterns of community biogeography, assembly, and co-occurrence.
Neuroprotective Effects of Tauroursodeoxicholic Acid Involves Vascular and Glial Changes in Retinitis Pigmentosa Model
Authors: Fernández-Sánchez Laura , Albertos-Arranz Henar , Ortuño-Lizarán Isabel , Lax Pedro , Cuenca Nicolás
Published: April 2022

Purpose

Retinitis pigmentosa is primarily characterized by a massive photoreceptor loss. But a global retinal remodeling occurs in later stages of the disease. At that phase, glial cells and retinal vasculature are also strongly affected. The main aim of the present work is to assess if the bile acid Tauroursodeoxicholic acid (TUDCA), which has a demonstrated neuroprotective effect in numerous neurodegenerative diseases, is able to prevent glial and vascular degeneration in the P23H rat retina.

Methods

Homozygous P23H (line 3) animals were injected weekly with a TUDCA (500 mg/kg, i.p.) or vehicle solution, from the postnatal day (P) 21 to P120. Sprague-Dawley rats (SD) were used as control. Retinal cross-sections and wholemounts were immunostained using different glial and vascular markers and visualized with confocal microscopy. Retinal blood vessels were stained with nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry and retinal vascular networks were drawn by hand using a camera lucida.

Results

At P120, the photoreceptor degeneration observed in P23H rats was accompanied by a reduction in the vascular network density and complexity at the deep capillary plexus. In addition, astrocytes showed gliotic features and the outer processes of Müller cells displayed an aberrant distribution in ring-shaped structures. When treated with TUDCA, P23H rats displayed better-preserved vessels and capillary loops in the deep capillary plexus which are associated with the partial preservation of photoreceptors. TUDCA treatment also increased the number of astrocytes and reduced the presence of Müller cell process clusters in the outer retina.

Conclusion

This work suggests that, besides its neuroprotective effect on photoreceptor cells, TUDCA treatment also protects from vascular and glial degeneration, a fact that encourages the use of TUDCA as a powerful therapy for neurodegenerative diseases.
Raging Hormones: Why Age-Based Etiological Conceptualizations of the Development of Antisocial Behavior Are Insufficient
Authors: White Stuart F. , Estrada Gonzalez S. Mariely , Moriarty Eibhlis M.
Published: April 2022

Developmental science, particularly developmental neuroscience, has substantially influenced the modern legal system. However, this science has typically failed to consider the role of puberty and pubertal hormones on development when considering antisocial behavior. This review describes major theoretical positions on the developmental neuroscience of antisocial behavior and highlights where basic developmental neuroscience suggests that the role of puberty and pubertal hormones should be considered. The implications of the current state of the science with respect to developmental neuroscience is considered, particularly what is known in light of development beyond puberty. This review shows that development continues to an older age for many youth than the legal system typically acknowledges. The plasticity of the brain that this continued development implies has implications for the outcome of interventions in the legal system in ways that have not been explored. Future directions for both developmental scientists and legal professions are recommended.
Association Between Concussions and Suicidality in High School Students in the United States
Authors: Iverson Grant L. , Karr Justin E.
Published: April 2022

Importance

Prior research has shown a statistically significant association between sustaining a concussion and suicidality in adolescents, but this prior research controlled for relatively few variables predictive of suicidality.

Objective

To examine whether sustaining a concussion remained a significant predictor of suicidality after controlling for relevant covariates (e.g., sexual abuse/assault, bullying, substance use, depression), hypothesizing that the relationship between concussion and suicidality would become non-significant after controlling for these variables.

Design

This study involved secondary data analysis of the 2019 Youth Risk Behavior Surveillance (YRBS) System, a national cross-sectional study of adolescents. Analyses were stratified by gender.

Setting

A national sampling of U.S. high school students.

Participants

Eleven thousand two hundred sixty-two students in the YRBS database, including 5,483 boys and 5,779 girls.

Exposure(s)

Participants included in the analyses reported whether, in the last year, they experienced a concussion and/or suicidality.

Main Outcomes and Measures

The main outcome was suicidality (i.e., ideation, planning, attempt), which was predicted by concussion in an unadjusted analysis and by concussion along with other risk factors in a multivariable analysis.

Results

The final sample included 11,262 participants with available data on concussion and suicidality in the last year (14–18 years-old; 51.3% girls; 49.0% White). Per unadjusted odds ratios with 95% confidence intervals, there was a relationship between concussion and suicidal ideation [girls: OR = 1.46 (1.24, 1.73); boys: OR = 1.69 (1.41, 2.03)], planning (girls: OR = 1.39 [1.16, 1.66]; boys: OR = 1.76 [1.44, 2.14]), and attempt [girls: OR = 1.70 (1.32, 2.19); boys: OR = 3.13, (2.37, 4.15)]. These relationships became mostly non-significant after controlling for relevant risk factors for suicidality. The adjusted odds ratios showed no relationship between concussion and suicidal ideation [girls: OR = 1.11 (0.86, 1.44); boys: OR = 1.24 (0.92, 1.69)] or planning (girls: OR = 1.07 [0.82, 1.40]; boys: OR = 1.12 [0.82, 1.55]); but a significant relationship with suicide attempts in boys [OR = 1.98 (1.28, 3.04)], but not girls [OR = 1.05 (0.74, 1.49)].

Conclusions and Relevance

There was an association between concussion and suicidality in U.S. high school students; however, after controlling for other variables (e.g., depression, sexual abuse/assault, illicit drug use), there was no association between concussion and suicidality aside from a significant relationship between concussion and attempts in boys.
The Association Between Precuneus Function and Residual Dizziness in Patients With Benign Paroxysmal Positional Vertigo
Authors: Fu Wei , Bai Ya , He Feng , Wei Dong , Wang Yuanyuan , Shi Ying , An Xinyue , Han Junliang , Wang Xiaoming
Published: April 2022

Objectives

The purpose of this study was to apply the amplitude of the low-frequency fluctuation (ALFF) method to investigate the spontaneous brain activity alterations in patients with residual dizziness (RD) after successful canalith repositioning manoeuvre for benign paroxysmal positional vertigo (BPPV).

Methods

All BPPV patients underwent visual vertigo analog scale (VVAS) evaluations and functional magnetic resonance imaging (fMRI). The ALFF method was used to assess the spontaneous brain activity. Screening of brain regions with significant changes in ALFF values was based on analysis of the whole brain. We further analyze the relationship between ALFF values of the altered regions and VVAS scores in BPPV patients with RD.

Results

Fifteen BPPV patients with RD and fifteen without RD were recruited in this study. In contrast to without RD, RD patients exhibited increased scores in VVAS tests (p < 0.001) and RD patients also showed significant ALFF decrease in the bilateral precuneus (left: 251 voxels; x = −10, y = −69, z = 51; peak t-value = −3.25; right: 170 voxels; x = 4, y = −59, z = 42; peak t-value = −3.43). Correlation analysis revealed that the mean ALFF z-values in the left precuneus displayed significant negative correlations with the VVAS scores(r = −0.44, p = 0.01).

Conclusions

This study shows that RD is associated with left precuneus function as revealed by fMRI. It might provide useful information for explaining neural mechanisms in BPPV patients with RD.
Egocentric Chunking in the Predictive Brain: A Cognitive Basis of Expert Performance in High-Speed Sports
Authors: Lappi Otto
Published: April 2022

What principles and mechanisms allow humans to encode complex 3D information, and how can it be so fast, so accurately and so flexibly transformed into coordinated action? How do these processes work when developed to the limit of human physiological and cognitive capacity—as they are in high-speed sports, such as alpine skiing or motor racing? High-speed sports present not only physical challenges, but present some of the biggest perceptual-cognitive demands for the brain. The skill of these elite athletes is in many ways an attractive model for studying human performance “in the wild”, and its neurocognitive basis. This article presents a framework theory for how these abilities may be realized in high-speed sports. It draws on a careful analysis of the case of the motorsport athlete, as well as theoretical concepts from: (1) cognitive neuroscience of wayfinding, steering, and driving; (2) cognitive psychology of expertise; (3) cognitive modeling and machine learning; (4) human-in-the loop modellling in vehicle system dynamics and human performance engineering; (5) experimental research (in the laboratory and in the field) on human visual guidance. The distinctive contribution is the way these are integrated, and the concept ofchunkingis used in a novel way to analyze a high-speed sport. The mechanisms invoked are domain-general, and not specific to motorsport or the use of a particular type of vehicle (or any vehicle for that matter); theegocentric chunking hypothesisshould therefore apply to any dynamic task that requires similar core skills. It offers a framework for neuroscientists, psychologists, engineers, and computer scientists working in the field of expert sports performance, and may be useful in translating fundamental research into theory-based insight and recommendations for improving real-world elite performance. Specific experimental predictions and applicability of the hypotheses to other sports are discussed.
Clinical Basis for Creating an Osseointegrated Neural Interface
Authors: Karczewski Alison M. , Zeng Weifeng , Stratchko Lindsay M. , Bachus Kent N. , Poore Samuel O. , Dingle Aaron M.
Published: April 2022

As technology continues to improve within the neuroprosthetic landscape, there has been a paradigm shift in the approach to amputation and surgical implementation of haptic neural prosthesis for limb restoration. The Osseointegrated Neural Interface (ONI) is a proposed solution involving the transposition of terminal nerves into the medullary canal of long bones. This design combines concepts of neuroma formation and prevention with osseointegration to provide a stable environment for conduction of neural signals for sophisticated prosthetic control. While this concept has previously been explored in animal models, it has yet to be explored in humans. This anatomic study used three upper limb and three lower limb cadavers to assess the clinical feasibility of creating an ONI in humans. Anatomical measurement of the major peripheral nerves- circumference, length, and depth- were performed as they are critical for electrode design and rerouting of the nerves into the long bones. CT imaging was used for morphologic bone evaluation and virtual implantation of two osseointegrated implants were performed to assess the amount of residual medullary space available for housing the neural interfacing hardware. Use of a small stem osseointegrated implant was found to reduce bone removal and provide more intramedullary space than a traditional implant; however, the higher the amputation site, the less medullary space was available regardless of implant type. Thus the stability of the endoprosthesis must be maximized while still maintaining enough residual space for the interface components. The results from this study provide an anatomic basis required for establishing a clinically applicable ONI in humans. They may serve as a guide for surgical implementation of an osseointegrated endoprosthesis with intramedullary electrodes for prosthetic control.
Cortical Tracking of Sung Speech in Adults vs Infants: A Developmental Analysis
Authors: Attaheri Adam , Panayiotou Dimitris , Phillips Alessia , Ní Choisdealbha Áine , Di Liberto Giovanni M. , Rocha Sinead , Brusini Perrine , Mead Natasha , Flanagan Sheila , Olawole-Scott Helen , Goswami Usha
Published: April 2022

Here we duplicate a neural tracking paradigm, previously published with infants (aged 4 to 11 months), with adult participants, in order to explore potential developmental similarities and differences in entrainment. Adults listened and watched passively as nursery rhymes were sung or chanted in infant-directed speech. Whole-head EEG (128 channels) was recorded, and cortical tracking of the sung speech in the delta (0.5–4 Hz), theta (4–8 Hz) and alpha (8–12 Hz) frequency bands was computed using linear decoders (multivariate Temporal Response Function models, mTRFs). Phase-amplitude coupling (PAC) was also computed to assess whether delta and theta phases temporally organize higher-frequency amplitudes for adults in the same pattern as found in the infant brain. Similar to previous infant participants, the adults showed significant cortical tracking of the sung speech in both delta and theta bands. However, the frequencies associated with peaks in stimulus-induced spectral power (PSD) in the two populations were different. PAC was also different in the adults compared to the infants. PAC was stronger for theta- versus delta- driven coupling in adults but was equal for delta- versus theta-driven coupling in infants. Adults also showed a stimulus-induced increase in low alpha power that was absent in infants. This may suggest adult recruitment of other cognitive processes, possibly related to comprehension or attention. The comparative data suggest that while infant and adult brains utilize essentially the same cortical mechanisms to track linguistic input, the operation of and interplay between these mechanisms may change with age and language experience.
Transcranial Magnetic Stimulation and Neocortical Neurons: The Micro-Macro Connection
Authors: Tian Dongting , Izumi Shin-Ichi
Published: April 2022

Understanding the operation of cortical circuits is an important and necessary task in both neuroscience and neurorehabilitation. The functioning of the neocortex results from integrative neuronal activity, which can be probed non-invasively by transcranial magnetic stimulation (TMS). Despite a clear indication of the direct involvement of cortical neurons in TMS, no explicit connection model has been made between the microscopic neuronal landscape and the macroscopic TMS outcome. Here we have performed an integrative review of multidisciplinary evidence regarding motor cortex neurocytology and TMS-related neurophysiology with the aim of elucidating the micro–macro connections underlying TMS. Neurocytological evidence from animal and human studies has been reviewed to describe the landscape of the cortical neurons covering the taxonomy, morphology, circuit wiring, and excitatory–inhibitory balance. Evidence from TMS studies in healthy humans is discussed, with emphasis on the TMS pulse and paradigm selectivity that reflect the underlying neural circuitry constitution. As a result, we propose a preliminary neuronal model of the human motor cortex and then link the TMS mechanisms with the neuronal model by stimulus intensity, direction of induced current, and paired-pulse timing. As TMS bears great developmental potential for both a probe and modulator of neural network activity and neurotransmission, the connection model will act as a foundation for future combined studies of neurocytology and neurophysiology, as well as the technical advances and application of TMS.
The Effects of Single Strains and Mixtures of Probiotic Bacteria on Immune Profile in Liver, Spleen, and Peripheral Blood
Authors: Fong Fiona Long Yan , El-Nezami Hani , Mykkänen Otto , Kirjavainen Pirkka V.
Published: April 2022

Probiotic bacteria have potential use as immunomodulators but comparative data on their immunological effects are very limited. The aim of this study was to characterize the effect of oral administration of probiotic strains, alone or as mixtures, on systemic and organ-specific immune responses. For this purpose, healthy C57BL/6 mice were perorally administered probiotics for 3 weeks. A total of five common probiotic strains, Lactobacillus rhamnosus species GG (LGG) and LC705, Bifidobacterium breve 99 (Bb99), Propionibacterium freudenreichii Shermanii JS (PJS), and Escherichia coli Nissle 1917 (EcN), and two of their mixtures, were tested. Livers, spleens, and blood were collected for investigation. A number of five treatments increased the abundance of the natural killer (NK) cells. Bb99 had the most prominent effect on hepatic NK cells (20.0 ± 1.8%). LGG (liver: 5.8 ± 1.0%; spleen: 1.6 ± 0.4%), Bb99 (liver: 13.9 ± 4.3%; spleen: 10.3 ± 3.7%), and EcN (liver: 8.5 ± 3.2%; spleen: 1.0 ± 0.2%) increased the percentage of both the hepatic and splenic T-helper 17 cells. Moreover, LGG (85.5 ± 3.0%) and EcN (89.6 ± 1.2%) increased the percentage of splenic regulatory T-cells. The tested mixtures of the probiotics had different immunological effects from their individual components on cell-mediated responses and cytokine production. In conclusion, our results confirm that the immunomodulatory potential of the probiotics is strain- and organ/tissue-specific, and the effects of probiotic mixtures cannot be predicted based on their single constituents.
Association Between Water Intake and Mortality Risk—Evidence From a National Prospective Study
Authors: Zhou Hao-long , Wei Mu-hong , Cui Yuan , Di Dong-sheng , Song Wen-jing , Zhang Ru-yi , Liu Jun-an , Wang Qi
Published: April 2022

Background

Few studies have explored the association between water intake and mortality risk, and the findings were inconsistent.

Objective

This study aimed to explore the water intake–mortality association, utilizing the data from the National Health and Nutrition Examination Survey (NHANES) and the 2015 public-linked mortality files released by the National Center for Health Statistics.

Methods

We used the diet- and mortality-linked data of a total of 35,463 adults (17,234 men) aged ≥20 years in the NHANESs 1999–2014 to perform a prospective study. The multivariate-adjusted Cox proportional hazards model was used to explore the associations of the amount of water intake (expressed by total water, plain water, beverage, and food water) and water intake proportion (expressed by the percentage of each kind of water) with mortality risks due to all causes, malignant neoplasms/cancer, and heart disease. The restricted cubic spline plots were adopted to clarify the dose–response relationships among them.

Results

With a median of 88 months (interquartile range: 49–136 months) follow-up, a total of 4,915 all-cause deaths occurred, including 1,073 and 861 deaths from malignant neoplasms/cancer and heart disease, respectively. The amount of water intake in either type was negatively associated with all-cause mortality risk. Additionally, the negative linear dose–response relationships of water intake and all-cause mortality risk were found for all types of water except for food water, which followed a non-linear pattern. Similarly, compared to the lowest quartile (beverage water intake: <676 g/day; food water intake: <532 g/day), beverage and food water intakes in the range of 1,033–1,524 and 1,612–3,802 g/day were associated with decreased malignant neoplasms/cancer mortality risk. A U-shaped dose–response relationship was found for beverage water intake and malignant neoplasms/cancer mortality risk and a negative linear dose–response relationship was found for food water intake and malignant neoplasms/cancer mortality risk. Coffee and/or tea consumption was/were negatively associated with mortality risks due to all causes and malignant neoplasms/cancer. No significant associations of water intake proportion and mortality risks were found.

Conclusion

Our findings demonstrated that higher water intake is associated with lower mortality risks among the United States population.
Dietary Patterns in Pregnancy and Biomarkers of Oxidative Stress in Mothers and Offspring: The NELA Birth Cohort
Authors: Morales Eva , García-Serna Azahara M. , Larqué Elvira , Sánchez-Campillo María , Serrano-Munera Ana , Martinez-Graciá Carmen , Santaella-Pascual Marina , Suárez-Martínez Clara , Vioque Jesús , Noguera-Velasco José A. , Avilés-Plaza Francisco V. , Martínez-Villanueva Miriam , Ballesteros-Meseguer Carmen , Galdo-Castiñeira Lina , García-Marcos Luis
Published: April 2022

Background

Although adherence to the Mediterranean and antioxidant-rich diets during pregnancy is suggested to improve maternal-fetal health by reducing oxidative stress, yet there is no study available.

Objective

We examined whether maternal dietary patterns in pregnancy impact the biomarkers of oxidative stress in mothers and their offspring.

Methods

Study population included 642 mothers and 335 newborns of the “Nutrition in Early Life and Asthma” (NELA) birth cohort. Maternal diet during pregnancy was assessed by a validated food frequency questionnaire and a priori-defined dietary indices (relative Mediterranean Diet [rMED], alternative Mediterranean Diet [aMED], Dietary Approach to Stop Hypertension [DASH], Alternate Healthy Index [AHEI], and AHEI-2010) were calculated. Biomarkers measured were: hydroperoxides, carbonyl groups, and 8-hydroxydeoxyguanosine (8OHdG) determined in maternal blood and newborn cord blood, and urinary maternal and offspring 15-F2t-isoprostane. Multivariate linear regression models were performed.

Results

Maternal rMED score was inversely associated with the maternal levels of 8OHdG at mid-pregnancy (beta per 1-point increase = −1.61; 95% CI −2.82, −0.39) and the newborn levels of hydroperoxides (beta per 1-point increase = −4.54; 95% CI −9.32, 0.25). High vs. low maternal rMED score was marginally associated with the decreased levels of 8OHdG in newborns (beta = −9.17; 95% CI −19.9, 1.63; p for trend 0.079). Maternal DASH score tended to be inversely associated with maternal urinary 15-F2t-isoprostane (beta per 1-point increase = −0.69; 95% CI, −1.44, 0.06). High vs. low maternal AHEI score was associated with reduced offspring urinary levels of 15-F2t-isoprostane (beta = −20.2; 95% CI −38.0, −2.46; p for trend 0.026).

Conclusion

These results suggest that maternal adherence to healthy dietary patterns during pregnancy may reduce DNA damage and lipid oxidation in mothers and offspring.
Quality-of-Life Outcomes in Female Patients With Ileal Conduit or Orthotopic Neobladder Urinary Diversion: 6-Month Results of a Multicenter Prospective Study
Authors: Siracusano Salvatore , Zaka Agustina , Bassi Pierfrancesco , Gontero Paolo , Mearini Ettore , Imbimbo Ciro , Simonato Alchiede , Dal Moro Fabrizio , Giannarini Gianluca , Valotto Claudio , Montorsi Francesco , Colombo Renzo , Porpiglia Francesco , Bartoletti Riccardo , Vella Marco , Minervini Andrea , Porcaro Antonio Benito , Romantini Federico , Vicentini Carlo , Talamini Renato , Ficarra Vincenzo , Lonardi Cristina
Published: April 2022

Radical cystectomy (RC) often affects patients’ life as this surgery is a traumatic and invasive event for the patients, with drawbacks on their daily, social, working, and sex life. Such changes in the quality of life (QoL) of patients are commonly studied through retrospective clinical evaluations and rarely with longitudinal studies. To date, studies focusing on functional outcomes, sexual function, and health-related QoL for female patients are lacking. We evaluated 37 patients using EORTC QLQ-C30 (QLQ-30) and Short-Form 36 (SF-36) questionnaires, before and after surgery, at 3 and 6 months of follow-up. The mean values for the emotional functioning in QLQ-C30 as well as the mental health in SF-36 were significantly higher in the ONB group compared to the IC group at 3 months of follow-up. These differences were not significant at 6 months of follow-up. At 6 months of follow-up, the ONB group showed a higher mean score in the physical and role functioning than the IC group. Although there was a statistically significant age difference at baseline of the two groups, none of the results are correlated with age, as demonstrated by Spearman’s analysis. The ONB seems to represent the most advantageous solution compared to the IC in terms of QOL at the 6-month follow-up.
Cerebral Oxygenation in Preterm Infants Developing Cerebral Lesions
Authors: Schwab Angelika L. , Mayer Benjamin , Bassler Dirk , Hummler Helmut D. , Fuchs Hans W. , Bryant Manuel B.
Published: April 2022

Background

We investigated the association between cerebral tissue oxygen saturation (cStO2) measured by near-infrared spectroscopy (NIRS) and cerebral lesions including intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL).

Methods

Preterm infants <1,500 g received continuous cStO2 monitoring, initiated at the earliest time possible and recorded until 72 h of life. Mean cStO2 over periods of 5, 15, 30 min and 1 h were calculated. To calculate the burden of cerebral hypoxia, we defined a moving threshold based on the 10th percentile of cStO2 of healthy study participants and calculated the area under the threshold (AUT). cStO2 <60% for >5 min was regarded a critical event. The study was registered on clinicaltrials.gov (ID NCT01430728, URL: https://clinicaltrials.gov/ct2/show/NCT01430728?id=NCT01430728&draw=2&rank=1).

Results

Of 162 infants (gestational age: mean 27.2 weeks, standard deviation 20 days; birth weight: mean 852 g, standard deviation 312 g) recorded, 24/12 (14.8%/7.4) developed any/severe IVH/PVL. Mean cStO2 was significantly lower in infants with IVH/PVL as well as severe IVH/PVL. In addition, we observed critical events defined by mean cStO2 over 5 min <60% in four infants with severe IVH/PVL during NIRS monitoring. AUT showed no statistically significant difference between outcome groups.

Conclusion

These findings suggest that cStO2 is lower in infants developing IVH/PVL. This may be related to lower oxygenation and/or perfusion and implies that cStO2 could potentially serve as an indicator of imminent cerebral lesions.
Tocilizumab and Abatacept for the Treatment of Childhood Chronic Uveitis: A Monocentric Comparison Experience
Authors: Maccora Ilaria , Abu Rumeileh Sarah , Curci Franco , de Libero Cinzia , Marrani Edoardo , Mastrolia Maria Vincenza , Pagnini Ilaria , Simonini Gabriele
Published: April 2022

Background

Our study aimed to evaluate the efficacy of Tocilizumab and Abatacept for treating Childhood Chronic non-infectious Uveitis (CCU), resistant to anti-tumor necrosis factor (anti-TNF) treatment.

Methods

This is a monocentric retrospective charts review study (January 2010–April 2021) recruiting CCU, refractory to anti-TNF. To be included, children should have active uveitis at the time of Tocilizumab (8 mg/kg, every 4 weeks) or Abatacept (10 mg/kg, every 4 weeks). The main outcome was the achievement of ocular remission on treatment defined as the absence of flares for ≥ 6 months.

Results

In this study, 18 patients with CCU (14 F), previously treated with Methotrexate and Adalimumab, were enrolled: 15 had juvenile idiopathic arthritis (JIA) (83.3%), 2 idiopathic (11.1%), and 1 Behçet (5.6%). Furthermore, ten patients received Abatacept and 8 patients received Tocilizumab. The mean duration of treatment on Abatacept was 31.6 months (SD ± 30.8), on Tocilizumab 25.25 months (SD ± 17.8). In total, 13 children (72.2%) achieved remission, with a better remission rate for the Tocilizumab group (8/8) compared to the Abatacept group (5/10) (χ2 5.53, p = 0.019). No difference was evaluated between the two groups in the proportion of patients who showed flares during the treatment (2/6 Abatacept vs. 1/8 Tocilizumab). A significant difference was evaluated in the proportion of patients who flared after treatment discontinuation: 3/3 Abatacept vs. 0/3 Tocilizumab (χ2 3.8, p = 0.025).

Conclusion

Even though this is a monocentric retrospective study, in a relatively small group, our study suggests a superior efficacy of Tocilizumab over Abatacept for treating anti-TNF refractory CCU.
Practical Considerations of PRN Medicines Management: An Integrative Systematic Review
Authors: Mardani Abbas , Paal Piret , Weck Christiane , Jamshed Shazia , Vaismoradi Mojtaba
Published: April 2022

Background and objectives: Highly widespread use of pro re nata (PRN) medicines in various healthcare settings is a potential area for improper medication prescription and administration leading to patient harm. This study aimed to summarize and integrate the findings of all relevant individual studies regarding the practical considerations of PRN medicines management including strategies and interventions by healthcare professionals for safe prescription, dispensing, administration, monitoring, and deprescription of PRN medicines in healthcare settings.

Methods: An integrative systematic review on international databases were performed. Electronic databases including Web of Knowledge, Scopus, PubMed (including MEDLINE), and Cinahl were searched to retrieve articles published until end of May 2021. Original qualitative, quantitative, and mixed methods studies written in English were included with a focus on PRN medicines management in healthcare settings. Research synthesis using the narrative method was performed to summarise the results of included studies.

Results: Thirty-one studies on PRN medicines in healthcare settings by different healthcare providers were included after the screening of the databases based on eligibility criteria. They were published from 1987 to 2021. The majority of studies were from Australia, the United States, Canada, and the United Kingdom and were conducted in psychiatric settings. Given variations in their purposes, methods, and outcomes, the research synthesis was conducted narratively based on diversities and similarities in findings. Eight categories were developed by the authors as follows: “PRN indications and precautionary measures,” “requirements of PRN prescription,” “interventions for PRN administration,” “monitoring and follow up interventions,” “deprescription strategies,” “healthcare professionals’ role,” “participation of patients and families,” and “multidisciplinary collaboration.” Each category consists of several items and describes what factors should be considered by healthcare professionals for PRN medicines management.

Conclusion: The review findings provide insights on the practical considerations of PRN medicines management in clinical practice. The suggested list of considerations in our review can be used by healthcare professionals for optimal PRN medicines management and safeguarding patient care.
Effects of Maren Pills on the Intestinal Microflora and Short-Chain Fatty Acid Profile in Drug-Induced Slow Transit Constipation Model Rats
Authors: Zhan Yu , Wen Yong , Du Li-juan , Wang Xiao-xiang , Tang Shi-yu , Kong Peng-fei , Huang Wei-guo , Tang Xue-gui
Published: April 2022

Background: Slow transit constipation (STC) is becoming a common and frequently occurring disease in today’s society, and it is necessary to explore the safe and effective treatment of STC.

Method: Our study aimed to investigate whether the laxative effect of Maren pills (MRW) is associated with the regulation of intestinal microflora and intestinal metabolism in the colon. Loperamide hydrochloride-induced STC rats received MRW intragastrically for two consecutive weeks to evaluate the laxative effect of MRW involving the regulation of intestinal microflora, intestinal metabolism, and 5-HT signaling pathway. Intestinal microflora was detected by 16s rDNA sequencing, intestinal metabolism of short-chain fatty acids (SCFAs) was detected by HPLC, and the 5-HT signaling pathway was detected by WB, ELISA, immunofluorescence, and immunohistochemical analysis.

Results: Our results revealed that the treatments with MRW increased not only the body weight, 24-h fecal number, 24-h wet fecal weight, 24-h dry fecal weight, fecal water content, and the intestinal propulsion rate but also the colonic goblet cell number, colonic Muc-2 protein expression, and colonic mucus layer thickness in the STC model rats. Moreover, MRW activated the 5-HT pathway by increasing the levels of 5-HT, 5-HIAA, 5-HT4R, CFTR, cAMP, and PKA in the colon tissue of STC rats. The 16S rDNA sequencing results showed that MRW improved the colonic microflora structure in colonic contents of STC rats, mainly by increasing Lactobacillus and decreasing Prevotella. Finally, we found that MRW regulated the SCFA metabolism in the colonic contents of the STC rats, mainly by increasing the contents of acetic acid, propionic acid, and butyric acid; the relative abundance of Lactobacillus was positively correlated with either contents of acetic acid, propionic acid, and butyric acid, and the relative abundance of Clostridium was negatively correlated.

Conclusion: Our study further showed that MRW could improve constipation in STC rats, and the mechanism may be by regulating the intestinal microflora structure and improving the metabolism of SCFAs.