bluuebunny/crossref_metadata_2025 huggingface dataset:
Facile method for immobilization of protein on elastic nanofibrous polymer membranes
Authors: Roh Soonjong , Lee Kangwon , Jung Youngmee , Yoo Jin
Published: March 2023

Surface modification of polymeric scaffolds for biomedical applications is a versatile and widely used method to improve interactions between scaffolds and cells. Specifically, chemical immobilization of proteins to polymeric scaffolds provides significant advantages such as stable and biocompatible properties, however, it generally requires expensive instruments or complex steps. In this study, the facile method is presented that changes poly (l-lactide-co-caprolactone) electrospun nanofibrous membranes to be cell-friendly and bioactive by chemical immobilization of proteins onto membranes. The model protein, bovine serum albumin was bound onto the nanofibrous membranes via aminolysis and subsequent covalent grafting. The surface modification effects of the nanofibrous membranes including surface morphologies, mechanical properties, and wettability were investigated. In addition, in vitro studies have demonstrated that adhesion and proliferation of human dermal fibroblasts are promoted in protein-immobilized membranes compared to bare nanofibrous membranes.
Development and implementation of a comprehensive ultrasound curriculum for medical students: The Bonn internship point-of-care-ultrasound curriculum (BI-POCUS)
Authors: Recker Florian , Schäfer Valentin Sebastian , Holzgreve Wolfgang , Brossart Peter , Petzinna Simon
Published: March 2023

Background

Point-of-care ultrasound (POCUS) is rapidly gaining ground within different areas of applications. Despite the high and increasing relevance of ultrasound, the availability of structured training programs in medical schools is still limited. Therefore, many doctors keep acquiring all their ultrasound skills throughout their postgraduate training. As a result, new residents lack theoretical and practical ultrasound abilities that are critical in everyday clinical practice. In order to improve this, we created and implemented a complete ultrasound curriculum for all medical students throughout their internship year that focuses on hands-on abilities in ultrasound imaging.

Methods

We used Kern‘s six-step model of curricular development comprising (1) problem identification and general needs assessment, (2) needs assessment of the targeted learners, (3) goals and objectives, (4) educational strategies, (5) implementation, and (6) evaluation and feedback by board-certified ultrasound experts. A two rounds Delphi process with multilevel, self-completed questionnaires and individual using a 9-point Likert scale and free text comments was used to identify learning objectives and reach agreement on the content of the curriculum.

Results

The curriculum developed is aimed at students with no or little experience in their internship year and will be taught as part of their weekly-based internship training courses consisting of 2 hours of theory and 3 hours of practical training. The training will be conducted within a modular framework focusing on the key requirements of POCUS with increasing levels of complexity in accordance with the recommendations of the German Society for Ultrasound in Medicine (DEGUM), the European Federation of Societies for ultrasound in Medicine and Biology (EFSUMB) and the World Federation for ultrasound in Medicine and Biology (WFUMB). A longitudinal e-learning system will be implemented in addition to the practical and theoretical teaching units to track and examine the progress of the students.

Conclusion

Early integration of ultrasound training into medical education as part of a structured and standardized broad ultrasound curriculum enables medical students to acquire basic skills and apply them practically. Fundamental scanning skills are acquired by hands-on exercises in small, supervised groups as part of BI-POCUS. BI-POCUS therefore provides an excellent opportunity to improve the clinical skills of future physicians. More research is needed to analyze the learning outcomes for medical students and the improvement of the patient’s outcome by establishing such an ultrasound curriculum.
Effectiveness of mid-regional pro-adrenomedullin, compared to other biomarkers (including lymphocyte subpopulations and immunoglobulins), as a prognostic biomarker in COVID-19 critically ill patients: New evidence from a 15-month observational prospective study
Authors: Montrucchio Giorgia , Sales Gabriele , Balzani Eleonora , Lombardo Davide , Giaccone Alice , Cantù Giulia , D'Antonio Giulia , Rumbolo Francesca , Corcione Silvia , Simonetti Umberto , Bonetto Chiara , Zanierato Marinella , Fanelli Vito , Filippini Claudia , Mengozzi Giulio , Brazzi Luca
Published: March 2023

Background

Mid-regional pro-adrenomedullin (MR-proADM), an endothelium-related peptide, is a predictor of death and multi-organ failure in respiratory infections and sepsis and seems to be effective in identifying COVID-19 severe forms. The study aims to evaluate the effectiveness of MR-proADM in comparison to routine inflammatory biomarkers, lymphocyte subpopulations, and immunoglobulin (Ig) at an intensive care unit (ICU) admission and over time in predicting mortality in patients with severe COVID-19.

Methods

All adult patients with COVID-19 pneumonia admitted between March 2020 and June 2021 in the ICUs of a university hospital in Italy were enrolled. MR-proADM, lymphocyte subpopulations, Ig, and routine laboratory tests were measured within 48 h and on days 3 and 7. The log-rank test was used to compare survival curves with MR-proADM cutoff value of >1.5 nmol/L. Predictive ability was compared using the area under the curve (AUC) and 95% confidence interval (CI) of different receiver-operating characteristic curves.

Results

A total of 209 patients, with high clinical severity [SOFA 7, IQR 4–9; SAPS II 52, IQR 41–59; median viral pneumonia mortality score (MuLBSTA)−11, IQR 9–13] were enrolled. ICU and overall mortality were 55.5 and 60.8%, respectively. Procalcitonin, lactate dehydrogenase, D-dimer, the N-terminal prohormone of brain natriuretic peptide, myoglobin, troponin, neutrophil count, lymphocyte count, and natural killer lymphocyte count were significantly different between survivors and non-survivors, while lymphocyte subpopulations and Ig were not different in the two groups. MR-proADM was significantly higher in non-survivors (1.17 ± 0.73 vs. 2.31 ± 2.63, p < 0.0001). A value of >1.5 nmol/L was an independent risk factor for mortality at day 28 [odds ratio of 1.9 (95% CI: 1.220–3.060)] after adjusting for age, lactate at admission, SOFA, MuLBSTA, superinfections, cardiovascular disease, and respiratory disease. On days 3 and 7 of the ICU stay, the MR-proADM trend evaluated within 48 h of admission maintained a correlation with mortality (p < 0.0001). Compared to all other biomarkers considered, the MR-proADM value within 48 h had the best accuracy in predicting mortality at day 28 [AUC = 0.695 (95% CI: 0.624–0.759)].

Conclusion

MR-proADM seems to be the best biomarker for the stratification of mortality risk in critically ill patients with COVID-19. The Ig levels and lymphocyte subpopulations (except for natural killers) seem not to be correlated with mortality. Larger, multicentric studies are needed to confirm these findings.
Comparison of the effects of probiotics, rifaximin, and lactulose in the treatment of minimal hepatic encephalopathy and gut microbiota
Authors: Wang Ming-Wei , Ma Wei-Juan , Wang Yan , Ma Xiao-Han , Xue Yu-Feng , Guan Jing , Chen Xi
Published: March 2023

Background

Minimal hepatic encephalopathy (MHE) is an early stage in the pathogenesis of hepatic encephalopathy. Intestinal microbiota is involved in the pathogenesis of hepatic encephalopathy and has become an important therapeutic target. Since there is no unified treatment principle for MHE, this study was conducted to determine the safety and efficacy of different intestinal microecological modulators in the treatment of MHE, and to explore the potential mechanism through intestinal microbiota analysis.

Methods

Patients with liver cirrhosis were screened for MHE using psychometric hepatic encephalopathy score test. Patients diagnosed with MHE were enrolled and received probiotics, rifaximin, or lactulose for 4 weeks. Adverse events were recorded. The psychometric hepatic encephalopathy score test was performed after treatment. Samples of blood and stool were collected at entry and 4 weeks. Blood samples were analyzed to assess blood ammonia, liver, kidney, and hemostatic functions. Stool microbiota were sequenced to confirm changes in microbial composition.

Results

Of 323 patients with liver cirrhosis, 74 patients were diagnosed with MHE. In all, 54 patients were enrolled and 52 who agree to follow-up were included in analysis. The recovery rates of MHE patients received probiotics, rifaximin, and lactulose were 58.8% (20/34), 45.5% (5/11), and 57.1% (4/7), respectively. Probiotics and rifaximin improved liver function in MHE patients to a certain extent. Taxonomic compositions of gut microbiota in MHE patients were distinct from healthy people before treatment; the differences were significantly reduced after treatment, and the gut microbiota gradually resembled the structure of healthy individuals. We found that the relative abundance of specific taxa associated with anti-inflammatory and good cognitive functions was increased in MHE patients after treatment. Accordingly, metabolic pathways in MHE patients were altered before and after treatment. Downregulated pathways after probiotics treatment included glycometabolism and degradation of aromatic compounds. After lactulose treatment, degradation pathways of arginine and ornithine showed a downward trend.

Conclusion

Probiotics, rifaximin, and lactulose are safe and effective in the treatment of MHE, and improve the composition of gut microbiota to some extent.
Association between behavioral and psychological symptoms and cerebral small vessel disease MRI findings in memory clinic patients
Authors: Shinohara Masaki , Matsuda Kana , Ii Yuichiro , Tabei Ken-ichi , Nakamura Naoko , Hirata Yoshinori , Ishikawa Hidehiro , Matsuyama Hirofumi , Matsuura Keita , Maeda Masayuki , Tomimoto Hidekazu , Shindo Akihiro
Published: March 2023

Objectives

Cerebral small vessel disease (SVD) is commonly observed among elderly individuals with cognitive impairment and has been recognized as a vascular contributor to dementia and behavioral and psychological symptoms (BPS), however, the relationship between BPS and SVD burden remains unclear.

Methods

We prospectively recruited 42 patients with mild cognitive impairment (MCI) or mild dementia from the memory clinic in our hospital, who were assigned to either a clinical dementia rating (CDR) of 0.5 or 1.0, respectively. The presence of BPS was determined through interviews with caregivers. The patients underwent brain MRI and three types of SVD scores, total, cerebral amyloid angiopathy (CAA), and modified CAA, were assigned. Patients were also evaluated through various neuropsychological assessments.

Results

The CDR was significantly higher in patients with BPS (p = 0.001). The use of antihypertensive agents was significantly higher in patients without BPS (p = 0.038). The time taken to complete trail making test set-A was also significantly longer in patients with BPS (p = 0.037). There was no significant difference in total SVD and CAA-SVD score (p = 0.745, and 0.096) and the modified CAA-SVD score was significantly higher in patients with BPS (p = 0.046). In addition, the number of total CMBs and lobar CMBs was significantly higher in patients with BPS (p = 0.001 and 0.001). Receiver operating characteristic curves for BPS showed that for modified CAA-SVD, a cutoff score of 3.5 showed 46.7% sensitivity and 81.5% specificity. Meanwhile, for the total number of cerebral microbleeds (CMBs), a cut-off score of 2.5 showed 80.0% sensitivity and 77.8% specificity and for the number of lobar CMBs, a cut-off score of 2.5 showed 73.3% sensitivity and 77.8% specificity.

Conclusion

Overall, patients with BPS showed worse CDRs, reduced psychomotor speed, higher modified CAA-SVD scores, larger numbers of total and lobar CMBs. We propose that severe modified CAA scores and higher numbers of total and lobar CMBs are potential risk factors for BPS in patients with mild dementia or MCI. Therefore, by preventing these MRI lesions, the risk of BPS may be mitigated.
Microgeometrical dendritic factors predict electrical decoupling between somatic and dendritic compartments in magnocellular neurosecretory neurons
Authors: Korogod Sergiy M. , Stern Javier E. , Cymbalyuk Gennady S.
Published: March 2023

It is generally assumed that dendritic release of neuropeptides from magnocellular neurosecretory neurons (MNNs), a critical process involved in homeostatic functions, is an activity-dependent process that requires backpropagating action potentials (APs). Still, growing evidence indicates that dendritic release can occur in the absence of APs, and axonal APs have been shown to fail to evoke dendritic release. These inconsistencies strongly suggest that APs in MNNs may fail to backpropagating into dendrites. Here we tested whether simple factors of electrical signal attenuation could lead to effective decoupling between cell’s body and dendritic release site within typical geometrical characteristics of MNN. We developed a family of linear mathematical models of MNNs and evaluated whether the somato-dendritic transfer of electrical signals is influenced by the geometrical characteristics. We determined the prerequisites for critically strong dendritic attenuation of the somatic input which are sufficient to explain the failure of APs initiated in the soma to backpropagating into dendritic compartments. Being measured in 100 μm from soma voltage attenuations down to 0.1 and 0.01 of the input value were chosen as the markers of electrical decoupling of dendritic sites from the soma, considering 0.1 insufficient for triggering dendritic spikes and 0.01 indistinguishable from background noise. The tested micro-geometrical factors were the dendritic stem diameter, varicosities, and size of peri-dendritic space limited by glial sheath wrapping. Varicosities increased the attenuation along homogeneous proximal dendrites by providing an increased current leak at the junction with the proximal dendritic section. The glial sheath wrapping a dendrite section promoted greater attenuation by increasing longitudinal resistance of the interstitial peri-dendritic space thus playing the insulating role. These decoupling effects were strengthened in the case of the dendritic stems with thinner diameters of and/or increased conductivity of the membrane. These micro-geometrical factors are biophysically realistic and predict electrical decoupling between somatic and dendritic compartments in MNNs.
Developmental regulation of GABAergic gene expression in forebrain cholinergic neurons
Authors: Granger Adam J. , Mao Karen , Saulnier Jessica L. , Hines Morgan E. , Sabatini Bernardo L.
Published: March 2023

Acetylcholine and GABA are often co-released, including from VIP-expressing neurons of the cortex, cortically-projecting neurons of the globus pallidus externus and basal forebrain, and hippocampal-projecting neurons of the medial septum. The co-release of the functionally antagonistic neurotransmitters GABA and acetylcholine (ACh) greatly expands the possible functional effects of cholinergic neurons and provides an additional exogenous source of inhibition to the cortex. Transgene expression suggests that nearly all forebrain cholinergic neurons in mice at some point in development express Slc32a1, which encodes the vesicular GABA transporter (VGAT). To determine the degree of co-expression of GABA and Ach handling proteins, we measured expression in adult mice of Slc32a1, Gad1 and Gad2 (which encode GAD67 and GAD65, respectively, the GABA synthetic enzymes) in cholinergic neurons using fluorescent in situ hybridization. We found that only a subset of cholinergic neurons express the necessary machinery for GABA release at a single time in adult mice. This suggests that GABA co-release from cholinergic neurons is dynamic and potentially developmentally regulated. By measuring expression of Slc32a1, Gad1, Gad2, and Chat in the basal forebrain and medial septum in mice from post-natal day 0 to 28, we noted abundant yet variable expressions of GABAergic markers across early development, which are subsequently downregulated in adulthood. This is in contrast with the forebrain-projecting pedunculopontine nucleus, which showed no evidence of co-expression of GABAergic genes. These results suggest that expression of GABA signaling machinery in the cortically-projecting cholinergic system peaks during early development before settling at a non-zero level that is maintained through adulthood.
Spatial distribution of heterogeneity as a modulator of collective dynamics in pancreatic beta-cell networks and beyond
Authors: Galvis Daniel , Hodson David J. , Wedgwood Kyle C. A.
Published: March 2023

We study the impact of spatial distribution of heterogeneity on collective dynamics in gap-junction coupled beta-cell networks comprised on cells from two populations that differ in their intrinsic excitability. Initially, these populations are uniformly and randomly distributed throughout the networks. We develop and apply an iterative algorithm for perturbing the arrangement of the network such that cells from the same population are increasingly likely to be adjacent to one another. We find that the global input strength, or network drive, necessary to transition the network from a state of quiescence to a state of synchronised and oscillatory activity decreases as network sortedness increases. Moreover, for weak coupling, we find that regimes of partial synchronisation and wave propagation arise, which depend both on network drive and network sortedness. We then demonstrate the utility of this algorithm for studying the distribution of heterogeneity in general networks, for which we use Watts–Strogatz networks as a case study. This work highlights the importance of heterogeneity in node dynamics in establishing collective rhythms in complex, excitable networks and has implications for a wide range of real-world systems that exhibit such heterogeneity.
Effects of wearable visual cueing on gait pattern and stability in patients with Parkinson’s disease
Authors: Zhang Wei , Han Yun , Shi Yuanyuan , Yan Shilei , Song Wenjing , Cui Guiyun , Xiang Jie
Published: March 2023

The present study examined the effects of wearable visual cues, provided by a wearable laser device, on the gait pattern and stability in patients with Parkinson’s disease (PD). In total, 18 patients with a clinical diagnosis of idiopathic PD (Hoehn and Yahr stage II-III) and 18 healthy controls were included. The main outcome measures included spatiotemporal parameters, sagittal plane kinematic parameters of joints in lower limbs, and dynamic center of pressure (COP) parameters. Significant intra-group improvement in gait parameters was observed in PD patients. Compared with that at baseline, the gait pattern improved in PD patients under the cued condition, with longer stride length and higher toe clearance, as well as shortening of double stance phase, especially the stride length, double stance phase and toe clearance were not significantly different between cued condition and healthy control groups. In kinematics, the ankle peak dorsiflexion in swing phase and the hip range of motion (ROM) in gait cycle was significantly improved in PD patients with visual cues and close to healthy controls. Decreased anteroposterior (AP) position of COP improved gait stability in patients with PD under the cued condition. Multiple linear regression analysis showed that the AP position has a negative correlation with ankle peak dorsiflexion in swing phase. Pearson’s correlation coefficients showed that the minimum toe clearance (Mini TC) was positively correlated with the ankle peak dorsiflexion in swing phase. The immediate effect of wearable visual cues improved the gait pattern and stability in PD patients, suggesting that it may be effective when applied as an alternative technique in rehabilitation training for PD patients.
EEG assessment of brain dysfunction for patients with chronic primary pain and depression under auditory oddball task
Authors: Li Yunzhe , Yang Banghua , Wang Zuowei , Huang Ruyan , Lu Xi , Bi Xiaoying , Zhou Shu
Published: March 2023

In 2019, the International Classification of Diseases 11th Revision International Classification of Diseases (ICD-11) put forward a new concept of “chronic primary pain” (CPP), a kind of chronic pain characterized by severe functional disability and emotional distress, which is a medical problem that deserves great attention. Although CPP is closely related to depressive disorder, its potential neural characteristics are still unclear. This paper collected EEG data from 67 subjects (23 healthy subjects, 22 patients with depression, and 22 patients with CPP) under the auditory oddball paradigm, systematically analyzed the brain network connection matrix and graph theory characteristic indicators, and classified the EEG and PLI matrices of three groups of people by frequency band based on deep learning. The results showed significant differences in brain network connectivity between CPP patients and depressive patients. Specifically, the connectivity within the frontoparietal network of the Theta band in CPP patients is significantly enhanced. The CNN classification model of EEG is better than that of PLI, with the highest accuracy of 85.01% in Gamma band in former and 79.64% in Theta band in later. We propose hyperexcitability in attentional control in CPP patients and provide a novel method for objective assessment of chronic primary pain.
Exploring the research landscape of COVID-19-induced olfactory dysfunction: A bibliometric study
Authors: Yang Zhirong , Ma Yukun , Bi Wei , Tang Jingqian
Published: March 2023

Since the outbreak of COVID-19, olfactory dysfunction (OD) has become an important and persistent legacy problem that seriously affects the quality of life. The purpose of this paper is to quantitatively analyze and visualize the current research status and development trend of COVID-19 related OD by using VOSviewer software. Based on the Web of Science database, a total of 1,592 relevant documents were retrieved in January 2023, with publication time spanning from 2020 to 2023. The bibliometric analysis revealed that the most influential research results in the field of COVID-19 related OD were concentrated in journals of related disciplines such as otorhinolaryngology, medicine, general and internal, virology, neurosciences, etc. The knowledge base of the research is mainly formed in two fields: COVID-19 clinical research and OD specialized research. The research hotspots are mainly concentrated in six directions: COVID-19, long COVID, smell, anosmia, OD, and recovery. Based on the results of the bibliometric analysis, the temporal trends of COVID-19 related OD studies were visually revealed, and relevant suggestions for future research were proposed.
Dodecyl creatine ester improves cognitive function and identifies key protein drivers including KIF1A and PLCB1 in a mouse model of creatine transporter deficiency
Authors: Mabondzo Aloïse , Harati Rania , Broca-Brisson Léa , Guyot Anne-Cécile , Costa Narciso , Cacciante Francesco , Putignano Elena , Baroncelli Laura , Skelton Matthew R. , Saab Cathy , Martini Emmanuelle , Benech Henri , Joudinaud Thomas , Gaillard Jean-Charles , Armengaud Jean , Hamoudi Rifat
Published: March 2023

Creatine transporter deficiency (CTD), a leading cause of intellectual disability is a result of the mutation in the gene encoding the creatine transporter SLC6A8, which prevents creatine uptake into the brain, causing mental retardation, expressive speech and language delay, autistic-like behavior and epilepsy. Preclinical in vitro and in vivo data indicate that dodecyl creatine ester (DCE) which increases the creatine brain content, might be a therapeutic option for CTD patients. To gain a better understanding of the pathophysiology and DCE treatment efficacy in CTD, this study focuses on the identification of biomarkers related to cognitive improvement in a Slc6a8 knockout mouse model (Slc6a8−/y) engineered to mimic the clinical features of CTD patients which have low brain creatine content. Shotgun proteomics analysis of 4,035 proteins in four different brain regions; the cerebellum, cortex, hippocampus (associated with cognitive functions) and brain stem, and muscle as a control, was performed in 24 mice. Comparison of the protein abundance in the four brain regions between DCE-treated intranasally Slc6a8−/y mice and wild type and DCE-treated Slc6a8−/y and vehicle group identified 14 biomarkers, shedding light on the mechanism of action of DCE. Integrative bioinformatics and statistical modeling identified key proteins in CTD, including KIF1A and PLCB1. The abundance of these proteins in the four brain regions was significantly correlated with both the object recognition and the Y-maze tests. Our findings suggest a major role for PLCB1, KIF1A, and associated molecules in the pathogenesis of CTD.
The protective effects of flavonoids and carotenoids against diabetic complications—A review of in vivo evidence
Authors: Jin Yannan , Arroo Randolph
Published: March 2023

Diabetes mellitus is a chronic metabolic disorder caused either by inadequate insulin secretion, impaired insulin function, or both. Uncontrolled diabetes is characterized by hyperglycemia which over time leads to fatal damage to both macro-and microvascular systems, causing complications such as cardiovascular diseases, retinopathy and nephropathy. Diabetes management is conventionally delivered through modifications of diet and lifestyle and pharmacological treatment, using antidiabetic drugs, and ultimately insulin injections. However, the side effects and financial cost of medications often reduce patient compliance to treatment, negatively affecting their health outcomes. Natural phytochemicals from edible plants such as fruits and vegetables (F&V) and medicinal herbs have drawn a growing interest as potential therapeutic agents for treating diabetes and preventing the onset and progression of diabetic complications. Flavonoids, the most abundant polyphenols in the human diet, have shown antidiabetic effects in numerous in vitro and preclinical studies. The underlying mechanisms have been linked to their antioxidant, anti-inflammatory and immunomodulatory activities. Carotenoids, another major group of dietary phytochemicals, have also shown antidiabetic potential in recent in vitro and in vivo experimental models, possibly through a mechanism of action similar to that of flavonoids. However, scientific evidence on the efficacy of these phytochemicals in treating diabetes or preventing the onset and progression of its complications in clinical settings is scarce, which delays the translation of animal study evidence to human applications and also limits the knowledge on their modes of actions in diabetes management. This review is aimed to highlight the potential roles of flavonoids and carotenoids in preventing or ameliorating diabetes-related complications based on in vivo study evidence, i.e., an array of preclinical animal studies and human intervention trials. The current general consensus of the underlying mechanisms of action exerted by both groups of phytochemicals is that their anti-inflammatory action is key. However, other potential mechanisms of action are considered. In total, 50 in vivo studies were selected for a review after a comprehensive database search via PubMed and ScienceDirect from January 2002 to August 2022. The key words used for analysis are type-2 diabetes (T2DM), diabetic complications, flavonoids, carotenoids, antioxidant, anti-inflammatory, mechanisms of prevention and amelioration, animal studies and human interventions.
Estimating the prevalence of exclusive breastfeeding with data from household surveys: Measurement issues and options
Authors: Pullum Thomas W. , Gribble Karleen , Mihrshahi Seema , Borg Bindi
Published: March 2023

The importance of breastfeeding for infant and maternal health is well established. The World Health Organization recommends that all infants be exclusively breastfed until they reach 6 months of age. The standard indicator to measure adherence to this criterion is the percentage of children aged 0–5 months who are currently being exclusively breastfed. This paper proposes supplementary measures that are easily calculated with existing survey data. First, for an accurate assessment of the WHO recommendation, we estimate the percentage of infants who are being exclusively breastfed at the exact age of 6 months. Second, an adjustment is proposed for prelacteal feeding. These two modifications, separately and in combination, are applied to data from 31 low-and middle-income countries that have participated in the Demographic and Health Surveys Program since 2015. There is considerable variation in the effects across countries. The modifications use existing data to provide a more accurate estimate than the standard indicator of the achievement of the exclusive breastfeeding until 6 months recommendation.
The efficacy and safety of an indocyanine green−hyaluronic acid mixture (LuminoMark™) for localization in patients with non-palpable breast lesions: A multicenter, randomized, open-label, parallel phase 3 clinical trial
Authors: Bang Yoon Ju , Choi Hee Jun , Kim Isaac , Lee Moo-Hyun , Lee Seeyoun , Shin Hyuk Jai , Nam Seok Jin , Lee Jeong Eon , Chae Byung-Joo , Lee Se Kyung , Ryu Jai Min , Kim Seok Won
Published: March 2023

Purpose

The incidence of early tumor detection is increasing due to popularization of breast cancer screening and the development of imaging techniques. Thus, suitable preoperative localization is required for proper diagnosis and treatment of non-palpable breast lesions. The purpose of this study was to evaluate the efficacy and safety of indocyanine green (ICG)-hyaluronic acid (HA) mixture for lesion localization compared to activated charcoal.

Methods

This was a multicenter, randomized, open-label, parallel phase 3 clinical trial performed at four centers in Korea. Female patients scheduled for surgery to remove non-palpable breast lesions were enrolled. One hundred and nine patients were randomly assigned to a control group (activated charcoal: 0.3. – 1 mL) or a study group (ICG-HA mixture, 0.2 mL) for the localization of a breast lesion. The primary endpoint was the accuracy of resection. Secondary endpoints included the technical success rate, histopathological accuracy, skin pigmentation rate, and adverse event rate.

Results

A total of 104 patients were eligible for per-protocol analysis (control group, n = 51; study group, n = 53). The accuracy of resection in the study group was not inferior to that of the control group (90.57% vs. 98.04%, 95% confidence interval (CI): -2.31 – 18.91, p = 0.21). There was no statistically significant difference in technical success rate between the two groups (marking on breast skin: p = 0.11, marking on the excised specimen: p = 0.12). However, there were statistically significant differences in histopathological accuracy (0.26 ± 0.13 vs. 0.33 ± 0.17, p = 0.01) and skin pigmentation rate (0.00% vs. 30.77%, p< 0.01). Adverse events were not reported in either group.

Conclusions

When localization was performed using ICG-HA, the accuracy of resection was not inferior to that of activated charcoal. However, skin pigmentation rate was significantly lower. In conclusion, ICG-HA is effective and safe for localizing of non-palpable breast lesions.
LncRNA LBX2-AS1 impacts osteosarcoma sensitivity to JQ-1 by sequestering miR-597-3p away from BRD4
Authors: Li Jiayu , Yuan Xuhui , Ma Cong , Li Junhong , Qu Gaoyang , Yu Bo , Cai Feng , Peng Yuanxiang , Liu Lang , Zeng Duo , Jiao QuanHui , Zhang Jiongfeng , Luo Xiaohui , Liao Qi , Lv Xiao-Bin
Published: March 2023

Objective

Recent knowledge concerning the significance of long non-coding RNA (lncRNA)-mediated ceRNA networks provides new insight into their possible roles as specific biomarkers for the treatment of osteosarcoma (OS). Thus, this study aims to clarify the functional relevance and mechanistic actions of lncRNA LBX2-AS1 in OS.

Methods

Differential analysis was performed by integrating the TCGA and GTEx databases. Cox regression analysis was then employed to assess the prognostic value of the model. The expression of lncRNA LBX2-AS1 and miR-597-3p was quantified in OS cell lines by qRT-PCR. The proliferation, migration, invasion, and apoptosis of OS cell lines in response to manipulated lncRNA LBX2-AS1 were evaluated by MTT, colony formation, transwell, Western blot, and flow cytometry assays. Luciferase activity was assayed to validate the reciprocal regulation between lncRNA LBX2-AS1 and miR-597-3p. The protein levels of BRD4 and EMT-related factors were examined by Western blot assay. Finally, tumor growth in response to LBX2-AS1 knockdown was evaluated in xenograft-bearing nude mice.

Results

By integrating the GTEx and TCGA databases, we identified 153 differentially expressed lncRNAs. Among them, 5 lncRNAs, RP11-535M15.1, AC002398.12, RP3-355L5.4, LBX2-AS1, and RP11.47A8.5, were selected to establish a model, which predicted the prognosis of OS. Higher lncRNA LBX2-AS1 expression was noted in OS tissues relative to that in normal tissues. Silencing lncRNA LBX2-AS1 facilitated apoptosis and curtailed proliferative, migratory, and invasive capacities of OS cells. Mechanistically, lncRNA LBX2-AS1 could elevate the expression of BRD4, an oncogene, by competitively binding to miR-597-3p. More importantly, knockdown of lncRNA LBX2-AS1 increased the sensitivity of OS cells to the BRD4 inhibitor JQ-1. Finally, the tumor growth of OS cell xenografts was constrained in vivo in the presence of lncRNA LBX2-AS1 knockdown.

Conclusion

In conclusion, lncRNA LBX2-AS1 promotes the growth of OS and represses the sensitivity to JQ-1 by sponging miR-597-3p to elevate the expression of BRD4.
Relationships between feeding and glucose concentrations in healthy term infants during the first five days after birth—the Glucose in Well Babies Study (GLOW)
Authors: Harris Deborah L , Weston Philip J. , Harding Jane E
Published: March 2023

Background

The World Health Organization recommends breastfeeding be commenced as soon as possible after birth. Amongst other benefits, early feeding is expected to support the metabolic transition after birth, but effects on blood glucose concentrations are controversial. We sought to describe the changes in interstitial glucose concentrations after feedings over the first five postnatal days.

Participants and Methods

In healthy singleton term infants, all feeds were recorded using a smart phone app. Glucose concentrations were measured by blinded interstitial monitoring, calibrated by heel-prick capillary samples 2–4 times/d. Feeding sessions were included if a start and end time were recorded, and if the interval between the start of successive feeds was >90 min. The area under the glucose concentration curve (AUC) was calculated by trapezoidal addition from baseline (median of the 3 measurements before the beginning of the session). The maximum deviation (MD) was the greatest change in glucose concentration (positive or negative) from baseline to the next feeding session or 180 min, whichever came first. Data were analyzed using Stata V17 and are presented as mean (95% CI) in mmol/L.

Results

Data were available for 62 infants and 1,770 feedings. The glucose response to breastfeeding was not different from zero on day 1 [day 1 AUC 0.05 (−0.00, 0.10), MD 0.06 (−0.05, 0.16)], but increased thereafter (day 3 (AUC 0.23 (0.18, 0.28), MD 0.41 (0.32, 0.50), day 5 AUC 0.11 (0.06, 0.16), MD 0.28 (0.18, 0.37), p < 0.001 for age effect). Glucose response increased with increased duration of breastfeeding (<30 min AUC 0.06 (0.02,0.09), MD 0.12 (0.04,0.19), >30 min AUC 0.20 (0.16, 0.23) MD 0.37 (0.30, 0.44), p < 0.001 for duration effect) and this was observed even in the first 2 days (<30 min AUC-0.02 (−0.06, 0.03), MD −0.06 (−0.15, 0.03), >30 min AUC 0.12 (0.08, 0.16), MD 0.19 (0.11, 0.27), overall p < 0.001 for age x duration interaction). In feeding sessions that were not breastfeeding, the glucose response was greater after formula than after expressed human milk [AUC 0.29 (0.15, 0.29), MD 0.48 (−0.12, 0.61)], and greater after feed volumes >20 ml than <10 ml [20–30 ml AUC 0.19 (0.01, 0.27), MD 0.23 (−0.01, 0.46)].

Conclusion

The glucose response to feeding in the days after birth increases with postnatal age and duration of the feeding episode. Breastfeeding for <30 min has little effect on glucose concentrations in the first two days.
Analysis of patient medication compliance and quality of life of physician-pharmacist collaborative clinics for T2DM management in primary healthcare in China: A mixed-methods study
Authors: Xiao Jie , Wang Qing , Tan Shenglan , Chen Lei , Tang Bingjie , Huang Shuting , Zhou Yangang , Xu Ping
Published: March 2023

Background: Physician-pharmacist collaboration is a well-established care mode for the management of type 2 diabetes mellitus (T2DM) in developed countries, but no study has been conducted in primary healthcare in China. This study aims to evaluate the effects of physician-pharmacist collaborative clinics to manage T2DM in primary healthcare in China, and to better understand the factors influencing the implementation of physician-pharmacist collaborative clinics.

Methods: Two hundred and sixty-seven patients involved in a 12-month randomized controlled trial were assigned to physician-pharmacist collaborative clinics and usual clinics, completing surveys regarding medication compliance, quality of life (QoL) and care-seeking behavior at the baseline, 3rd, 6th, 9th and 12th month respectively, and diabetes knowledge at baseline and 12th month. A sample of twenty-two Patients, nine physicians and twelve pharmacists participated in semi-structured face-to-face interviews. The quantitative and qualitative data was integrated by triangulation.

Results: Patients in physician-pharmacist collaborative clinics had significant improvements in medication compliance (p = 0.009), QoL (p = 0.036) and emergency visits (p = 0.003) over the 12-month. Pairwise comparison showed the medication compliance score in the intervention group had been significantly improved at 3rd month (p = 0.001), which is more rapidly than that in the control group at 9th month (p = 0.030). Factors influencing the implementation of physician-pharmacist collaborative clinics were driven by five themes: pharmaceutical service, team-base care, psychological support, acceptability of care and barriers to implementation.

Conclusion: Integration of quantitative and qualitative findings showed the effectiveness of physician-pharmacist collaborative clinics in patient medication compliance and QoL in primary healthcare. The qualitative study uncovered barriers in insufficient clinical experience and understaffing of pharmacist. Therefore, the professional training of the primary pharmacist team should be improved in the future.

Clinical Trial Registration:clinicaltrials.gov, identifier ChiCTR2000031839.
Risk factors associated with inappropriate empirical antimicrobial treatment in bloodstream infections. A cohort study
Authors: Dietl Beatriz , Boix-Palop Lucía , Gisbert Laura , Mateu Aina , Garreta Gemma , Xercavins Mariona , Badía Cristina , López-Sánchez María , Pérez Josefa , Calbo Esther
Published: March 2023

Introduction: Bloodstream infections (BSI) are a major cause of mortality all over the world. Inappropriate empirical antimicrobial treatment (i-EAT) impact on mortality has been largely reported. However, information on related factors for the election of i-EAT in the treatment of BSI in adults is lacking. The aim of the study was the identification of risk-factors associated with the use of i-EAT in BSI.

Methods: A retrospective, observational cohort study, from a prospective database was conducted in a 400-bed acute-care teaching hospital including all BSI episodes in adult patients between January and December 2018. The main outcome variable was EAT appropriation. Multivariate analysis using logistic regression was performed.

Results: 599 BSI episodes were included, 146 (24%) received i-EAT. Male gender, nosocomial and healthcare-associated acquisition of infection, a high Charlson Comorbidity Index (CCI) score and the isolation of multidrug resistant (MDR) microorganisms were more frequent in the i-EAT group. Adequation to local guidelines’ recommendations on EAT resulted in 91% of appropriate empirical antimicrobial treatment (a-EAT). Patients receiving i-EAT presented higher mortality rates at day 14 and 30 when compared to patients with a-EAT (14% vs. 6%, p = 0.002 and 22% vs. 9%, p < 0.001 respectively). In the multivariate analysis, a CCI score ≥3 (OR 1.90 (95% CI 1.16–3.12) p = 0.01) and the isolation of a multidrug resistant (MDR) microorganism (OR 3.79 (95% CI 2.28–6.30), p < 0.001) were found as independent risk factors for i-EAT. In contrast, female gender (OR 0.59 (95% CI 0.35–0.98), p = 0.04), a correct identification of clinical syndrome prior to antibiotics administration (OR 0.26 (95% CI 0.16–0.44), p < 0.001) and adherence to local guidelines (OR 0.22 (95% CI 0.13–0.38), p < 0.001) were identified as protective factors against i-EAT.

Conclusion: One quarter of BSI episodes received i-EAT. Some of the i-EAT related factors were unmodifiable (male gender, CCI score ≥3 and isolation of a MDR microorganism) but others (incorrect identification of clinical syndrome before starting EAT or the use of local guidelines for EAT) could be addressed to optimize the use of antimicrobials.
Metabolic stability and metabolite profiling of emerging synthetic cathinones
Authors: Lopes Rita P. , Ferro Raquel A. , Milhazes Margarida , Figueira Margarida , Caldeira Maria João , Antunes Alexandra M. M. , Gaspar Helena
Published: March 2023

Synthetic cathinones constitute the second largest groups of new psychoactive substances (NPS), which are especially popular among adolescents and young adults. Due to their potential toxicity, the recreational use of these NPS constitute a serious worldwide public health problem. However, their fast appearance in the market renders the continuous updating of NPS information highly challenging for forensic authorities. The unavailability of pharmacokinetic data for emerging NPS is critical for forensic and clinical verifications. With the ultimate goal of having a proactive approach towards the NPS issue, high resolution mass spectrometry was used in the current work to assess preliminary pharmacokinetic data for 8 selected cathinones: 4 reported substances (4-CIC, 3-CMC, 4-CMC and 4-MEAP) and 4 previously unreported ones (3-CIC, 4-MDMB, 4-MNEB and 4-MDMP) for which the emergence on the NSP market is expected to be eminent, were also included in this study. Based on the calculation of pharmacokinetic parameters, half-life and intrinsic clearance, 4-CMC and 4-MDMB are low and high clearance compounds, respectively, and all the remaining cathinones included in this study are intermediate clearance compounds. This fact anticipates the key role of metabolites as suitable biomarkers to extend detection windows beyond those provided by the parent cathinones. Reduction of the keto group and hydroxylation on the alkyl chains were the common metabolic pathways identified for all cathinones. However, the relative importance of these metabolic transformations is dependent on the cathinone substituents. The glucuronic acid conjugation to metabolites stemming for keto group reduction constituted the sole Phase II transformation identified. To our knowledge, this study constitutes the first metabolite profiling of the already reported synthetic cathinones 4-CIC, 3-CMC and 4-CMC. Noteworthy is the fact that 3-CMC accounts for almost a quarter of the quantity of powders seized during 2020. The analytical methods developed, and the metabolites characterized, are now available to be included in routine screening methods to attest the consumption of the 8 cathinones studied.
The protective effect and antitumor activity of Aconiti Lateralis Radix Praeparata (Fuzi) polysaccharide on cyclophosphamide-induced immunosuppression in H22 tumor-bearing mice
Authors: Hu Qi , Liu Yu , Yu Ji , Yang Xin , Yang Ming , He Yanan , Han Li , Zhang Dingkun
Published: March 2023

Background:Aconiti Lateralis Radix Praeparata, also known as Fuzi in Chinese, has been used in Traditional Chinese Medicine for more than 2,000 years. In recent years, some traditional herbal compounds containing Fuzi have achieved positive clinical results in tumor treatment. And the polysaccharide isolated from Fuzi has attracted much attention as a potential immunomodulator. However, its immunomodulatory mechanism remains to be further studied. Aim of the study. Fuzi neutral polysaccharide (FNPS) and cyclophosphamide (CTX) were combined to treat Hepatoma 22 (H22) tumor-bearing mice, and its mechanism of ameliorating immunosuppression caused by CTX was studied.

Methods: FNPS was isolated and purified. The molecular weight, functional groups, monosaccharide composition, and apparent morphology were characterized by gel permeation chromatography, Fourier transform infrared spectrometer, ion chromatography and scanning electron microscope, respectively. Through the analysis of tumor, immune organs, and serum cytokine levels of H22 tumor-bearing mice, the immunomodulatory effect and the protective effect on immunosuppressive mice induced by CTX was evaluated. And the immunomodulatory activity of FNPS was further verified by macrophage functional experiments.

Results: FNPS was composed of rhamnose, arabinose, galactose, glucose, and mannose in a molar ratio of 0.008:0.017:0.018:0.908:0.048. Its molecular weight was 94 kDa. In vivo experiments showed that 200 mg mL−1 FNPS could alleviate the suppression of immune organs and immune cells caused by CTX treatment, enhance the antitumor effect of CTX, increase the serum levels of Th1 immune-related pro-inflammatory cytokines (IL-1β and IL-6), and decrease Th2 immune-related anti-inflammatory cytokine (IL-10) and tumor-related pro-inflammatory cytokine (TNF-α) in the chemotherapy mice. Functional experiments revealed that 25 μg mL−1 FNPS could promote phagocytosis and proliferation of macrophages. When the concentration reached 50 μg mL−1, it enhanced the migration activity.

Conclusion: FNPS has the potential to alleviate the immunosuppressive effect of CTX by activating immune cells and promoting inflammation. It could be used as a potential auxiliary medication for liver cancer treatment.