bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobilizable plasmids drive the spread of antimicrobial resistance genes and virulence genes in Klebsiella pneumoniae
Authors: Zhang Jianfeng , Xu Yanping , Wang Meng , Li Xiaobin , Liu Zhiyuan , Kuang Dai , Deng Zixin , Ou Hong-Yu , Qu Jieming
Published: December 2023

Background

Klebsiella pneumoniae is a notorious clinical pathogen and frequently carries various plasmids, which are the main carriers of antimicrobial resistance and virulence genes. In comparison to self-transmissible conjugative plasmids, mobilizable plasmids have received much less attention due to their defects in conjugative elements. However, the contribution of mobilizable plasmids to the horizontal transfer of antimicrobial resistance genes and virulence genes of K. pneumoniae remains unclear. In this study, the transfer, stability, and cargo genes of the mobilizable plasmids of K. pneumoniae were examined via genetic experiments and genomic analysis.

Methods

Carbapenem-resistant (CR) plasmid pHSKP2 and multidrug-resistant (MDR) plasmid pHSKP3 of K. pneumoniae HS11286, virulence plasmid pRJF293 of K. pneumoniae RJF293 were employed in conjugation assays to assess the transfer ability of mobilizable plasmids. Mimic mobilizable plasmids and genetically modified plasmids were constructed to confirm the cotransfer models. The plasmid morphology was evaluated through XbaI and S1 nuclease pulsed-field gel electrophoresis and/or complete genome sequencing. Mobilizable plasmid stability in transconjugants was analyzed via serial passage culture. In addition, in silico genome analysis of 3923 plasmids of 1194 completely sequenced K. pneumoniae was performed to investigate the distribution of the conjugative elements, the cargo genes, and the targets of the CRISPR-Cas system. The mobilizable MDR plasmid and virulence plasmid of K. pneumoniae were investigated, which carry oriT but lack other conjugative elements.

Results

Our results showed that mobilizable MDR and virulence plasmids carrying oriT but lacking the relaxase gene were able to cotransfer with a helper conjugative CR plasmid across various Klebsiella and Escherichia coli strains. The transfer and stability of mobilizable plasmids rather than conjugative plasmids were not interfered with by the CRISPR–Cas system of recipient strains. According to the in silico analysis, the mobilizable plasmids carry about twenty percent of acquired antimicrobial resistance genes and more than seventy-five percent of virulence genes in K. pneumoniae.

Conclusions

Our work observed that a mobilizable MDR or virulence plasmid that carries oriT but lacks the relaxase genes transferred with the helper CR conjugative plasmid and mobilizable plasmids escaped from CRISPR–Cas defence and remained stable in recipients. These results highlight the threats of mobilizable plasmids as vital vehicles in the dissemination of antibiotic resistance and virulence genes in K. pneumoniae.
Collagen gene cluster expression and liver fibrogenesis in patients with biliary atresia: a preliminary study
Authors: Gunadi  , Puspitarani Dyah Ayu , Vujira Khanza Adzkia , Utami Fadila Dyah Trie , Devana Edita Mayda , Halim Fiqih Vidiantoro , Iskandar Kristy , Makhmudi Akhmad
Published: December 2023

Objective

Biliary atresia (BA) is a progressive fibro-obliterative disease of the biliary tract, which results in end-stage liver disease. However, liver fibrosis progression may continue even after Kasai surgery. Recent evidence showed that collagen plays a pivotal role in the progression of liver fibrosis in BA. However, most studies were conducted in developed countries. We investigated the expressions of the collagen gene cluster (COL6A1, COL6A2, COL6A3, and COL1A1) in BA patients in Indonesia.

Results

There was a significant down-regulated expression of COL6A1 (ΔCT 9.06 ± 2.64 vs. 5.42 ± 2.41; p = 0.0009), COL6A2 (ΔCT 8.25 ± 2.07 vs. 5.77 ± 3.51; p = 0.02), COL6A3 (ΔCT 11.2 ± 6.08 vs. 6.78 ± 3.51; p = 0.024), and COL1A1 (ΔCT 3.26 ± 1.71 vs. 0.19 ± 2.76; p = 0.0015) in BA patients compared to controls. Interestingly, the collagen gene cluster expressions were significantly associated with the presence of cirrhosis (p = 0.0085, 0.04, and 0.0283 for COL6A1, COL6A2, and COL6A3, respectively). In conclusion, our study shows the changes in the collagen gene cluster, particularly collagen type I and VI, expressions in patients with BA in a particular developing country. Our findings suggest the role of these collagen gene clusters in the liver fibrogenesis of BA.
A rapid and stable spontaneous reprogramming system of Spermatogonial stem cells to Pluripotent State
Authors: Wei Rui , Zhang Xiaoyu , Li Xiaoxiao , Wen Jian , Liu Hongyang , Fu Jiqiang , Li Li , Zhang Wenyi , Liu Zhen , Yang Yang , Zou Kang
Published: December 2023

Background

The scarcity of pluripotent stem cells poses a major challenge to the clinical application, given ethical and biosafety considerations. While germline stem cells commit to gamete differentiation throughout life, studies demonstrated the spontaneous acquisition of pluripotency by spermatogonial stem cells (SSCs) from neonatal testes at a low frequency (1 in 1.5 × 107). Notably, this process occurs without exogenous oncogenes or chemical supplementation. However, while knockout of the p53 gene accelerates the transformation of SSCs, it also increases risk and hampers their clinical use.

Results

We report a transformation system that efficiently and stably convert SSCs into pluripotent stem cells around 10 passages with the morphology similar to that of epiblast stem cells, which convert to embryonic stem (ES) cell-like colonies after change with ES medium. Epidermal growth factor (EGF), leukemia inhibitory factor (LIF) and fresh mouse embryonic fibroblast feeder (MEF) are essential for transformation, and addition of 2i (CHIR99021 and PD0325901) further enhanced the pluripotency. Transcriptome analysis revealed that EGF activated the RAS signaling pathway and inhibited p38 to initiate transformation, and synergically cooperated with LIF to promote the transformation.

Conclusion

This system established an efficient and safe resource of pluripotent cells from autologous germline, and provide new avenues for regenerative medicine and animal cloning.
Uncoupling p38α nuclear and cytoplasmic functions and identification of two p38α phosphorylation sites on β-catenin: implications for the Wnt signaling pathway in CRC models
Authors: Lepore Signorile Martina , Fasano Candida , Forte Giovanna , De Marco Katia , Sanese Paola , Disciglio Vittoria , Di Nicola Elisabetta , Pantaleo Antonino , Simone Cristiano , Grossi Valentina
Published: December 2023

Background

Activation of the Wnt pathway has been linked to colorectal cancer (CRC). Previous reports suggest that Wnt3a can activate p38. Besides, p38α feeds into the canonical Wnt/β-catenin pathway by inhibiting GSK3β through phosphorylation. Recently, we identified p38α as a new druggable member of β-catenin chromatin-associated kinase complexes in CRC.

Methods

The functional relationship between p38α and β-catenin was characterized in CRC cells, patient-derived CRC stem cells, patient-derived tumor intestinal organoids, and in vivo models (C57BL/6-APCMin/+ mice). The role of p38α in β-catenin transcriptional activity was assessed by pharmacological inhibition with ralimetinib.

Results

We used the GSK3β inhibitor TWS-119, which promotes the activation of Wnt signaling, to uncouple p38α nuclear/cytoplasmatic functions in the Wnt pathway. Upon GSK3β inhibition, nuclear p38α phosphorylates β-catenin at residues S111 and T112, allowing its binding to promoter regions of Wnt target genes and the activation of a transcriptional program implicated in cancer progression. If p38α is pharmacologically inhibited in addition to GSK3β, β-catenin is prevented from promoting target gene transcription, which is expected to impair carcinogenesis.

Conclusions

p38α seems to play a dual role as a member of the β-catenin destruction complex and as a β-catenin chromatin-associated kinase in CRC. This finding may help elucidate mechanisms contributing to human colon tumor pathogenesis and devise new strategies for personalized CRC treatment.
Endophytic bacteria in the periglacial plant Potentilla fruticosa var. albicans are influenced by habitat type
Authors: Sonam Wangchen , Liu Yongqin , Guo Liangdong
Published: December 2023

Background

Microbial communities in different plant compartments are relatively independent entities. However, the influence of environmental factors on the microbial community in different compartments of periglacial plants remains unclear. In this study, we quantified the bacterial communities in the rhizosphere soil, as well as root and leaf endosphere compartments of a periglacial plant, Potentilla fruticosa var. albicans, using high-throughput DNA sequencing. Moreover, we evaluated the impacts of habitat types (glacier terminus zone, moraine ridge, and alpine meadow) on the bacterial community in different plant compartments of Potentilla fruticosa var. albicans.

Results

Our results showed that habitat type had a significant effect on the alpha diversity (Chao1 richness) of endophytic bacteria, but not on the rhizospheric bacteria. The community composition of rhizospheric and endophytic bacteria was significantly different across the three habitats, and habitat type had a greater effect on the endophytic bacteria than on rhizospheric bacteria. The contribution of rhizosphere soil to the root and leaf endophytes decreased with the transformation of habitats from glacier terminus zone to alpine meadow. In contrast, host selection pressure sequentially increased from the glacier terminus zone to the moraine ridge to the alpine meadow. Furthermore, we found that the bacterial co-occurrence network in the alpine meadow was more modular but had lower complexity and connectedness than that in the glacier terminus zone. The bacterial community was governed primarily by stochastic processes regardless of habitat type.

Conclusion

This study reveals that the diversity and composition of endophytic bacteria associated with Potentilla fruticosa var. albicans are more affected by habitat types than that of rhizospheric bacteria. Our study also demonstrates that the assembly patterns and co-occurrence patterns of bacterial communities associated with Potentilla fruticosa var. albicans vary by habitat type. These results advance the current understanding of community assembly and ecological interactions of microbial communities associated with periglacial plants.
Soil erosion modeling and sediment transport index analysis using USLE and GIS techniques in Ada’a watershed, Awash River Basin, Ethiopia
Authors: Tilahun Abayneh , Desta Hayal
Published: December 2023

Ethiopia faces a significant challenge in combating soil erosion. This study addresses the concern within Ada’a watershed of the Awash River basin. GIS and the Universal Soil Loss Equation (USLE) Model were used to predict soil loss and the sediment transport index (STI) in the Ada’a watershed of the Awash River basin. RUSLE model required intensive rainfall data registered continuously for 30 min, due to unavailability of this Rainfall data USLE model were preferred. Moreover, USLE model was chosen because of its straightforward methodology and accessibility to data. The study's objectives were to determine the mean annual soil loss rate, STI, and to identify and rank the most important erosion-prone spots for soil conservation planning. Using the interactive Spatial Analyst Tool Map Algebra Raster Calculator in the ArcGIS environment, the mean annual soil loss was estimated based on grid cells by multiplying the corresponding USLE factor values (R, K, LS, C, and P). The STI was also calculated on the Raster Calculator in ArcGIS using flow accumulation and slope gradients. The result shows that R, K, LS, C, and P factor values were estimated in the watershed as 344.9 to 879.65 MJ mm h−1 year−1, 0.11 to 0.38, 0% to 22.23%, 0 to 1, and 0.55 to 1, respectively. The overall annual soil loss in the watershed ranged from 0 to 457.4 tons ha−1 year−1. The Sediment Transport Index ranges from 0 to 856.193. The result implies there is increasing rate of soil losses and sediments observed at alarming rate. The highest rate of soil loss was found in the watershed’s lowest parts. Accordingly, sustainable erosion control mechanisms based on topography and land use types are highly recommended, especially in the upper part of the watershed.
Preoperative splenic area as a prognostic biomarker of early-stage non-small cell lung cancer
Authors: Liu Mengmei , Yan Guanghong , Li Yanli , You Ruiming , Liu Lizhu , Zhang Dafu , Yang Guangjun , Dong Xingxiang , Ding Yingying , Yan Shan , You Dingyun , Li Zhenhui
Published: December 2023

Background

The correlation between the preoperative splenic area measured on CT scans and the overall survival (OS) of early-stage non-small cell lung cancer (NSCLC) patients remains unclear.

Methods

A retrospective discovery cohort and validation cohort consisting of consecutive NSCLC patients who underwent resection and preoperative CT scans were created. The patients were divided into two groups based on the measurement of their preoperative splenic area: normal and abnormal. The Cox proportional hazard model was used to analyse the correlation between splenic area and OS.

Results

The discovery and validation cohorts included 2532 patients (1374 (54.27%) males; median (IQR) age 59 (52–66) years) and 608 patients (403 (66.28%) males; age 69 (62–76) years), respectively. Patients with a normal splenic area had a 6% higher 5-year OS (n = 727 (80%)) than patients with an abnormal splenic area (n = 1805 (74%)) (p = 0.007) in the discovery cohort. A similar result was obtained in the validation cohort. In the univariable analysis, the OS hazard ratios (HRs) for the patients with abnormal splenic areas were 1.32 (95% confidence interval (CI): 1.08, 1.61) in the discovery cohort and 1.59 (95% CI: 1.01, 2.50) in the validation cohort. Multivariable analysis demonstrated that abnormal splenic area was independent of shorter OS in the discovery (HR: 1.32, 95% CI: 1.08, 1.63) and validation cohorts (HR: 1.84, 95% CI: 1.12, 3.02).

Conclusion

Preoperative CT measurements of the splenic area serve as a prognostic indicator for early-stage NSCLC patients, offering a novel metric with potential implications for personalized therapeutic strategies in top-tier oncology research.
Evaluation of the accuracy of implant placement by using implant positional guide versus freehand: a prospective clinical study
Authors: Huang Lixuan , Liu Linfeng , Yang Shengtao , Khadka Prapti , Zhang Shiwen
Published: December 2023

Purpose

The aim of this study is to examine and compare the accuracy of implant placement using implant positional guide and freehand.

Methods

48 implants were placed in patients with single tooth loss with implant positional guide and freehand, respectively. The accuracy of implant placement was assessed by comparing the actual and planned position, including four parameters: coronal deviation, apical deviation, angular deviation, and vertical deviation.

Results

Comparing all the variables, it has been found that the implant positional guide is more accurate than the freehand. All parameters describing in the deviation were significantly lower in the implant positional guide group than the freehand.

Conclusions

The implant positional guide can act as a practicable tool for dental implant surgery. It is a promising technology that guarantees low cost and high precision in implant surgery. However, based on the restricted evidence from clinical studies, longer follow-up periods, larger population studies, and standardized experimental studies are required.

Trial registration CHICTR, ChiCTR2300071024. Registered 28 April 2023—CHICTR, ChiCTR2300071024. Registered 28 April 2023—Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=195424.
The use of projected autonomy in antenatal shared decision-making for periviable neonates: a qualitative study
Authors: Thorvilson Megan J. , Carroll Katherine , Kaemingk Bethany D. , Schaepe Karen S. , Collura Christopher A.
Published: December 2023

Background

In this study, we assessed the communication strategies used by neonatologists in antenatal consultations which may influence decision-making when determining whether to provide resuscitation or comfort measures only in the care of periviable neonates.

Methods

This study employed a qualitative study design using inductive thematic discourse analysis of ‘naturally occurring data’ in the form of antenatal conversations around resuscitation decisions at the grey zone of viability. The study occurred between February 2017 and June 2018 on a labor and delivery unit within a large Midwestern tertiary care hospital. Participants included 25 mothers who were admitted to the study hospital with anticipated delivery in the grey zone of viability and practicing neonatologists or neonatology fellows who partnered in antenatal consultation. We used a two-stage inductive analytic process to focus on how neonatologists’ discourses constructed SDM in antenatal consultations. First, we used a thematic discourse analysis to interpret the recurring patterns of meaning within the transcribed antenatal consultations, and second, we theorized the subsequent effects of these discourses on shaping the context of SDM in antenatal encounters.

Results

In this qualitative study, that included discourse analysis of real-time audio conversations in 25 antenatal consults, neonatologists used language that creates projected autonomy through (i) descriptions of fetal physiology (ii) development of the fetus’s presence, and (iii) fetal role in decision-making.

Conclusion

Discourse analysis of real-time audio conversations in antenatal consultations was revelatory of how various discursive patterns brought the fetus into decision-making, thus changing who is considered the key actor in SDM.
Arterial stiffness and hypertension
Authors: Kim Hack-Lyoung
Published: December 2023

Arterial stiffness and hypertension are closely related in pathophysiology. Chronic high blood pressure (BP) can lead to arterial wall damage by mechanical stress, endothelial dysfunction, increased inflammation, oxidative stress, and renin–angiotensin–aldosterone system (RAAS) activation. Hypertension also increases collagen fiber production and accelerates elastin fiber degradation. Stiffened arteries struggle with BP changes, raising systolic BP and pulse pressure. The resulting increased systolic pressure further hardens arteries, creating a harmful cycle of inflammation and calcification. Arterial stiffness data can predict target organ damage and future cardiovascular events in hypertensive patients. Thus, early detection of arterial stiffness aids in initiating preventive measures and treatment plans to protect against progression of vascular damage. While various methods exist for measuring arterial stiffness, pulse wave velocity is a non-invasive, simple measurement method that maximizes effectiveness. Healthy lifestyle changes, RAAS blockers, and statins are known to reduce arterial stiffness. Further research is needed to ascertain if improving arterial stiffness will enhance prognosis in hypertensive patients.

Graphical Abstract
Signet cell rectal carcinoma with prostatic involvement detected by FAPI-04 PET-MRI fusion
Authors: Prashanth K. Arun , Jain Deepti , Manikandan R. , Kalyan Suman , Velayutham Vimalraj , Surendran R.
Published: December 2023

A 60-year-old male patient diagnosed with mucinous adenocarcinoma of lower third of rectum underwent abdominoperineal resection and permanent colostomy followed by adjuvant chemotherapy. Response evaluation with F-18 FDG PET-CT showed a complete metabolic response. After 6 months, CEA levels started increasing and clinically a recurrence was suspected. A restaging FDG PET-CT showed no obvious malignant disease. Patient presented again within a month with complaints of urinary retention and haematuria. CEA levels were further elevated, and Ga-68 FAPI-04 (FAPI) PET-CT was performed. FAPI PET-CT revealed prostatic and seminal vesicle disease involvement. Additionally, an MRI of pelvis was done and fused with FAPI PET for confirmation of prostatic involvement.
Cardiovascular disease risk in early rheumatoid arthritis: the impact of cartilage oligomeric matrix protein (COMP) and disease activity
Authors: Rydell Emil , Jacobsson Lennart TH , Saxne Tore , Turesson Carl
Published: December 2023

Background

To investigate whether baseline serum cartilage oligomeric matrix protein (COMP), patient characteristics, traditional cardiovascular disease (CVD) risk factors and disease activity over time predict CVD, in early rheumatoid arthritis (RA).

Methods

This study included patients with early RA (< 12 months disease duration) (n = 233) recruited 1995–2005. Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression.

Results

A first ever diagnosis of CVD occurred in 70 patients, and CAD in 52. Age, sex, hypertension and diabetes predicted CVD and CAD. COMP was associated with increased risk of CVD and CAD [crude hazard ratios (HRs) per SD 1.45; 95% CI 1.17–1.80 and 1.51; 95% CI 1.18–1.92, respectively]. When adjusted for age, sex, hypertension, diabetes and ESR, results where similar but did not reach significance [HRs 1.32, 95% CI 0.99–1.74 and 1.35, 95% CI 0.99–1.86]. Baseline disease activity did not independently predict CVD. High DAS28 (> 5.1) at two years was associated with increased risk of subsequent CVD [adjusted HR 2.58; 95% CI 1.10–6.04] and CAD. ESR and CRP at two years as well as cumulative disease activity over 2 years independently predicted CVD and CAD.

Conclusion

COMP may be a novel predictor of CVD and CAD in RA. Active disease two years after RA diagnosis, as well as cumulative disease activity, was associated with increased risk of CVD and CAD, independent of traditional CVD risk factors. Awareness of the particularly increased CVD risk among difficult to treat patients is important in order to further reduce CVD in RA.
Research on privacy information retrieval model based on hybrid homomorphic encryption
Authors: Song Wei-tao , Zeng Guang , Zhang Wen-zheng , Tang Dian-hua
Published: December 2023

The computational complexity of privacy information retrieval protocols is often linearly related to database size. When the database size is large, the efficiency of privacy information retrieval protocols is relatively low. This paper designs an effective privacy information retrieval model based on hybrid fully homomorphic encryption. The assignment method is cleverly used to replace a large number of homomorphic encryption operations. At the same time, the multiplicative homomorphic encryption scheme is first used to deal with the large-scale serialization in the search, and then the fully homomorphic encryption scheme is used to deal with the remaining simple operations. The depth of operations supported by the fully homomorphic scheme no longer depends on the size of the database, but only needs to support the single homomorphic encryption scheme to decrypt the circuit depth. Based on this hybrid homomorphic encryption retrieval model, the efficiency of homomorphic privacy information retrieval model can be greatly improved.
Immediate, short-term, and long-term effects of balloon mitral valvuloplasty on the left atrial global longitudinal strain and its correlation to the outcomes in patients with severe rheumatic mitral stenosis
Authors: Setouhi Amr , Boshra Hesham , Askalany Hany , Farrag Hazem M. A.
Published: December 2023

Background

Left atrial global longitudinal strain (LA GLS) has been used as a new assessment tool for left atrial function. This article aims to investigate the effect of balloon mitral valvuloplasty (BMV) in patients with severe rheumatic mitral stenosis on LA GLS and its relation to the mitral valve area achieved after the procedure. The study included 95 patients with severe mitral stenosis who fulfilled the criteria for BMV (case group) and 80 normal healthy subjects (control group). All included participants underwent complete echocardiographic examinations. For the case group, LA GLS was assessed by 2D speckle-tracking Echocardiography before valvuloplasty, immediately after, within 24 h, at 6 months, and at 12 months, and the results were compared.

Results

The impaired left-atrium strain in patients with severe mitral stenosis was improved immediately after BMV, and the improvement continued at 6 and 12 months post-BMV (23.1% ± 4.2 vs. 36.0% ± 4.9, 36.2% ± 4.5, and 40.1% ± 9.5, respectively p < 0.01). After BMV, there was a significant decrease in left atrial volume (76.3 ± 12.4 ml/m2 vs. 68.6 ± 10.4 ml/m2, p < 0.01) and a significant increase in the area occupied by the mitral valve (1.02 ± 0.18 cm2 vs. 1.60 ± 0.31 cm, p < 0.01). The immediate LA GLS and the mitral valve area were positively correlated (r = 0.64, p < 0.01). Furthermore, the immediate LA GLS was associated with significantly improved function class (p < 0.01).

Conclusions

LA GLS can indicate left atrial (mainly reservoir) function. The improvement observed in patients after BMV may indicate that LA GLS can be used to evaluate the progress after BMV.

Trial registration: The study was approved by the local ethics committee of the Faculty of Medicine in Minia University (Registration No. MUFMIRB 324-4-2022). Institutional Review Board, Faculty of Medicine, Minia University, Egypt. 324-4-2022, 24 18 April, 2022.
Cell therapies for autism spectrum disorder: a systematic review of clinical applications
Authors: Akat Ayberk , Karaöz Erdal
Published: December 2023

Purpose

Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects patients’ ability to communicate, engage with others, and behave in certain ways. Despite the existence of several therapy possibilities, an effective treatment for ASD has not yet been identified. Cell therapies have been becoming increasingly recognized in recent years as a potential therapeutic approach for the management of ASD. Different types of cellular products are transplanted using different delivery methods as part of cell therapy, which has the ability to regulate the immune system, demonstrate paracrine, neuro-regenerative, anti-inflammatory, and anti-oxidative stress effects, as well as transfer healthy mitochondria. We have compared the results and findings of completed cell therapy clinical trials for the treatment of ASD in this systematic review.

Methods

A total of 547 studies were identified, in which 11 studies were found to be eligible to be included in this review as they were completed cell therapy clinical trials or clinical applications with quantitative results for the treatment of ASD patients.

Results

This systematic review provides an overview of clinical trials conducted with different types of cell therapy strategies for the treatment of ASD and their potential mechanisms of action. The limitations and future possibilities for this field of study, as well as the safety and efficacy of cell treatments in ASD, were reviewed.

Conclusion

Overall, the evidence suggests that various cell therapy methods may offer a novel and effective treatment option for individuals with ASD, although further research is needed to fully understand the optimal treatment strategy and therapeutic potential.
Inhibitory capacity of extracts and main constituents of hop flowers
Authors: do Nascimento Francisco Mateus Gomes , Marques Samuel Pedro Dantas , Trevisan Maria Teresa Salles , Owen Robert Wyn , Pereira Lucas Ramos , Lima Thales Caldas , de Sousa Anderson Freitas , Maia Carlos Eduardo Gonçalves
Published: December 2023

Background

Hops (Humulus lupulus Linn.) produce flowers that are used on an industrial scale to impart sensory properties to beer and have some pharmacologic properties already published in the literature. Gout, type 2 diabetes and Alzheimer’s are diseases the appearance/aggravation of which is related to the action of enzymes such as xanthine oxidase, α-glucosidase and acetylcholinesterase, respectively, which are associated with oxidative stress. Our hypothesis is that the extracts and chemical constituents isolated from the flowers of hops act as enzyme inhibitors and scavenge free radicals. Hexane and methanol extracts were obtained from flowers of different cultivars produced in Brazil and from commercial pellets, with the contents of bitter acids and xanthohumol determined by high-performance liquid chromatography (HPLC), after QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) extraction and were evaluated for their pharmacologic properties.

Results

The extracts and analytical standards showed a significant capacity against oxidative stress in all evaluated methods (DPPH·, ABTS·+, HO·). Xanthohumol and extracts with a high concentration of this compound demonstrated a strong capacity to inhibit the xanthine oxidase and significantly reduce the formation of uric acid. The results with the α-glucosidase revealed promising pharmacologic action for all samples, even more effective than the commercial drug (acarbose). The acetylcholinesterase inhibition assays were effective for hexane extracts and ICE-4, with values obtained close to the eserine.

Conclusion

It can be concluded with the results obtained that extracts and patterns of hop flowers showed promising potential to combat oxidative stress and complementary treatment of gout, type 2 diabetes and Alzheimer’s disease.
The effect of comprehensive rehabilitation on post-COVID-19 syndrome
Authors: Kesikburun Bilge , Ata Ayşe Merve , Borman Pınar , Özdemir Elif Esen , Becenen Elif , Metin Nurdan , Alemdaroğlu Ebru
Published: December 2023

Background

The present study aimed to investigate the efficacy of a comprehensive rehabilitation program on quality of life, anxiety, fatigue, and functional status in post-COVID-19 patients admitted to a specialized rehabilitation unit. The secondary objective of the study was to compare the differences between vaccinated and unvaccinated patients.

Results

The single-center prospective study was conducted. Demographics, comorbidities, vaccination, clinical signs and symptoms, and oxygen saturation were assessed. The rehabilitative protocol was created considering the condition of patients, age, the direct impact of COVID-19 on the systems, sequelae, severity of disease, and comorbidities. The comprehensive rehabilitation program through a multidisciplinary team is applied in a stepwise graded manner. The Nottingham Health Profile (NHP), Fatigue Severity Scale (FSS) The Functional Ambulation Categories (FAC), the modified Medical Research Council (mMRC), the Modified Borg Scale, post-COVID-19 Functional Status (PCFS) scale, Hospital Anxiety and Depression Scale (HADS), and the Barthel Index (BI) were used. In total, 39 patients (61.5% men, age 59.7.0 ± 15.6 years) participated in the study. They were discharged home after 37.5 ± 17.6 days stay in the hospital. The most frequently reported persistent symptoms were dyspnea (76.9%), fatigue (69.2%), and myalgia (64.1%). There was a statistically significant improvement in baseline outcomes including BI, HADS, PCFS, FSS, MMRC, Modified Borg Scale, FAC, O2 support, and NHP after the comprehensive rehabilitation program (p < 0.001). The vaccinated patients had older age, high BMI, and shorter duration of rehabilitation (p = 0.003, p = 0.040, p = 0.022, respectively), while unvaccinated patients had higher BI, FSS, PCFS, and FAC.

Conclusion

The comprehensive rehabilitation program improves quality of life, reduces fatigue, anxiety, and depression, and regains function in patients with post-COVID-19 syndrome. In addition, vaccinated patients had older ages and shorter duration of rehabilitation, while unvaccinated patients achieved higher functional status and had significantly higher levels of fatigue at discharge.
High versus standard blood pressure target in hypertensive high-risk patients undergoing elective major abdominal surgery: a study protocol for the HISTAP randomized clinical trial
Authors: Messina Antonio , Cortegiani Andrea , Romagnoli Stefano , Sotgiu Giovanni , Piccioni Federico , Donadello Katia , Girardis Massimo , Noto Alberto , Maggiore Salvatore Maurizio , Antonelli Massimo , Cecconi Maurizio
Published: December 2023

Background

The intraoperative period is often characterized by hemodynamic instability, and intraoperative hypotension is a common complication. The optimal mean arterial pressure (MAP) target in hypertensive patients is still not clear. We hereby describe the protocol and detailed statistical analysis plan for the high versus standard blood pressure target in hypertensive high-risk patients undergoing elective major abdominal surgery: the HISTAP randomized clinical trial. The HISTAP trial aims at addressing whether the use of a higher intraoperative MAP target in high-risk hypertensive surgical patients scheduled for elective abdominal surgery would improve postoperative outcomes, as compared to the standard and recommended perioperative MAP, by using a composite outcome including a 30-day mortality from surgical intervention and at least one major organ dysfunction or new onset of sepsis and septic shock occurring 7 days after surgery.

Methods

The HISTAP trial is an investigator-initiated, pragmatic, parallel-grouped, randomized, stratified, analyst-blinded trial with adequate allocation sequence generation, and allocation concealment. We will allocate 636 patients to a MAP target ≥ 80 mmHg (treatment group) or to a MAP target ≥65 mmHg (control group). The primary outcome is a composite outcome including a 30-day mortality from the operation and major organ complications. Secondary outcomes are mortality at 30 days, intensive care unit (ICU) length of stay, ICU readmission, Sequential Organ Failure Assessment (SOFA) scores recorded up to postoperative day 7, overall intraoperative fluid balance, vasopressors use, and the need for reoperation. An unadjusted χ2 test will be used for the primary outcome analysis. A Cox proportional hazards model will be used to adjust the association between the primary outcome and baseline covariates.

Conclusions

The HISTAP trial results will provide important evidence to guide clinicians’ choice regarding the intraoperative MAP target in high-risk hypertensive patients scheduled for elective abdominal surgery.
Health promotion, the social determinants of health, and urban health: what does a critical discourse analysis of World Health Organization texts reveal about health equity?
Authors: Amri Michelle , Enright Theresa , O’Campo Patricia , Di Ruggiero Erica , Siddiqi Arjumand , Bump Jesse Boardman
Published: December 2023

Background

The World Health Organization (WHO) has focused on health equity as part of its mandate and broader agenda—consider for example, the “health for all” slogan. However, a recent scoping review determined that there are no studies that investigate the WHO’s approach to health equity. Therefore, this study is the first such empirical analysis examining discourses of health equity in WHO texts concerning health promotion, the social determinants of health, and urban health.

Methods

We undertook a critical discourse analysis of select texts that concern health promotion, the social determinants of health, and urban health.

Results

The findings of this study suggest that (i) underpinning values are consistent in WHO texts’ approach to health equity; (ii) WHO texts reiterate that health inequities are socially constructed and mitigatable but leave the ‘causes of causes’ vague; (iii) despite distinguishing between health “inequities” and “inequalities,” there are several instances where these terms are used interchangeably across texts; (iv) WHO texts approach health equity broadly (covering a variety of areas); (v) health equity may be viewed as applicable either throughout the life-course or intergenerationally, which depends on the specific WHO text at hand; and (vi) WHO texts at times use vague or unclear language around how to improve health equity.

Conclusions

This study does not present one definition of health equity and action to be taken. Instead, this study uncovers discourses embedded in WHO texts to spur discussion and deliberate decision-making. This work can also pave the way for further inquiry on other complex key terms or those with embedded values.
Neuropsychiatric Adverse Effects of Synthetic Glucocorticoids: A Systematic Review and Meta-Analysis
Authors: Koning Anne-Sophie C A M , van der Meulen Merel , Schaap Daphne , Satoer Djaina D , Vinkers Christiaan H , van Rossum Elisabeth F C , van Furth Wouter R , Pereira Alberto M , Meijer Onno C , Dekkers Olaf M
Published: December 2023

Context

Synthetic glucocorticoids are widely used to treat patients with a broad range of diseases. While efficacious, glucocorticoids can be accompanied by neuropsychiatric adverse effects.

Objective

This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids.

Methods

Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort studies, and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and nonusers were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model.

Results

We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95% CI, 14%-33%), 11% for mania (2%-46%), 8% for anxiety (2%-25%), 16% for delirium (6%-36%), and 52% for behavioral changes (42%-61%). Questionnaire scores for depression (SMD of 0.80 [95% CI 0.35-1.26]), and mania (0.78 [0.14-1.42]) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use.

Conclusion

The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed.
Fahr Syndrome Secondary to Pseudohypoparathyroidism
Authors: Shu Sharon W , Sharma Sakshi , Iqbal Qasim Z , Romo Karina G
Published: December 2023

Fahr syndrome is a rare neurologic disorder, usually affecting young and middle-aged adults, that can present with symptoms ranging from extrapyramidal to neuropsychiatric abnormalities. Pseudohypoparathyroidism (PHP), characterized by parathyroid hormone (PTH)-resistance or PTH-unresponsiveness at target organs, is associated with Fahr syndrome and typically presents with hypocalcemia. The following case presents a 39-year-old-woman with PHP complicated by symptomatic hypocalcemia, hypokalemia, and movement disturbances, who had computed tomography imaging showing basal ganglia calcifications consistent with Fahr syndrome. She initially presented with headache and was hospitalized for hypertensive emergency and severe hypocalcemia. Examination, including the neurologic examination, was unrevealing aside from hypertension and central adiposity. Laboratory tests were consistent with PHP, showing hypocalcemia with elevated PTH, and negative for hyperaldosteronism. Management of hypocalcemia consisted of intravenous calcium infusion, oral calcium carbonate, oral vitamin D3, and oral calcitriol. Patients with severe hypocalcemia and elevated PTH who present with new neurological symptoms despite normal general neurologic examination may warrant consideration for brain imaging to evaluate for Fahr syndrome. Further investigations are necessary to determine the prevalence of Fahr syndrome and hypokalemia in patients with PHP, explore if these findings are significantly associated with PHP-1b subtype, and ultimately inform potential new screening pathways for these patients.
An Object In Between
Authors: Ma Xiaolu
Published: December 2023

By interrogating how the original composition and textual reincarnations of Lu Xun's “Diary of a Madman” manifest his idea of an “object in between,” this article celebrates an intertextual event in world literature. It traces how Lu Xun's “Diary of a Madman” came into being in conversation with preexisting literary creations and how the intertextual recasting of Lu Xun's story both within and beyond the Sinophone world incorporates postcolonial contexts and recent cyberculture. The intertextuality not only calls for a dynamic negotiation with Lu Xun's “Diary of a Madman” but also involves unexpected engagement with the literary antecedents to Lu Xun's work. By examining the transculturation of cannibalism and insanity in the works of Lu Xun, Liang Wern Fook, Ōe Kenzaburō, and Leonid Andreev, among others, this article reveals how “Diary of a Madman” as an object in between projects a vision of a future that resists the pressures of historical impasse.
Treatment of Acute Traumatic Central Cord Syndrome: A Study of North American Trauma Centers
Authors: Badhiwala Jetan H. , Witiw Christopher D. , Wilson Jefferson R. , da Costa Leodante B. , Nathens Avery B. , Fehlings Michael G.
Published: December 2023

BACKGROUND AND OBJECTIVES:

Central cord syndrome (CCS) is expected to become the most common traumatic spinal cord injury, yet its optimal management remains unclear. This study aimed to evaluate variability in nonoperative vs operative treatment for CCS between trauma centers in the American College of Surgeons Trauma Quality Improvement Program, identify patient- and hospital-level factors associated with treatment, and determine the association of treatment with outcomes.

METHODS:

Adults with CCS were identified from the Trauma Quality Improvement Program database (2014-2016). Mixed-effects modeling with a random intercept for trauma centers was used to examine the adjusted association of patient- and hospital-level variables with nonoperative treatment. The random-effects output of the model assessed the risk-adjusted variability in nonoperative treatment across centers. Outlier hospitals were identified, and the median odds ratio was calculated. The adjusted effect of nonoperative treatment on mortality, morbidity, and hospital length of stay (LOS) was examined at the patient and hospital level by mixed-effects regression.

RESULTS:

Three thousand, nine hundred twenty-eight patients across 255 centers were eligible; of these, 1523 (38.8%) were treated nonoperatively. Older age, noncommercial insurance (odds ratio [OR] 1.26, 95% CI 1.08-1.48, P = .004), absence of fracture (OR 0.58, 95% CI 0.49-0.68, P < .001), severe head injury (OR 1.41, 95% CI 1.09-1.82, P = .008), and comatose presentation (1.82, 95% CI 1.15-2.89, P = .011) were associated with nonoperative treatment. Twenty-eight hospitals were outliers, and the median odds ratio was 2.02. Patients receiving nonoperative treatment had shorter LOS (mean difference −4.65 days). Nonoperative treatment was associated with lesser in-hospital morbidity (OR 0.49, 95% CI 0.37-0.63, P < .001) at the patient level. There was no difference in mortality.

CONCLUSION:

Operative decision-making for CCS is influenced by patient factors. There remains substantial variability between trauma centers not explained by case-mix differences. Nonoperative treatment was associated with shorter hospital LOS and lesser inpatient morbidity.
Woven EndoBridge Device for Unruptured Wide-Neck Bifurcation Aneurysm: A Multicenter 5-Year Follow-up
Authors: Semeraro Vittorio , Palmisano Vitanio , Limbucci Nicola , Comelli Simone , Comelli Chiara , Ganimede Maria Porzia , Lozupone Emilio , Barone Michele , Marrazzo Antonio , Paladini Andrea , della Malva Giuseppina , Briatico Vangosa Alessandra , Laiso Antonio , Renieri Leonardo , Capasso Francesco , Gandini Roberto , Di Stasi Carmine , Resta Maurizio , Mangiafico Salvatore , Burdi Nicola
Published: December 2023

BACKGROUND AND OBJECTIVES:

This multicenter study aimed to assess the safety and efficacy of the Woven EndoBridge (WEB) device for treating unruptured wide-neck intracranial bifurcation aneurysms (WIBAs) with short-, mid-, and long-term follow-ups (FUPs).

METHODS:

Consecutive patients with unruptured WIBAs treated with WEB between December 2014 and January 2018 were included. Patient, aneurysm, and device characteristics were collected and analyzed retrospectively. Morbidity and mortality rates were determined by collecting intraprocedural, periprocedural, and delayed complications. Aneurysm occlusion was assessed at 1, 3, and 5 years using a 3-grade scale: complete occlusion, neck remnant, and residual aneurysm. Complete occlusion and neck remnant were considered as adequate occlusion. Patients who received re-treatment were also evaluated.

RESULTS:

The study included 104 consecutive patients (55.8% female, mean age 58.6 ± 11.8 years). Aneurysm maximum size, neck, and dome-to-neck mean were, respectively, 6.9 ± 2.1 mm, 4.5 ± 1.2 mm, and 1.4 ± 0.3 mm. One-year FUP was collected for 95 patients, and 3- and 5-year FUPs were collected for 83 patients. Adequate occlusion was observed at 1-year FUP in 90.5% (86/95), 91.6% (76/83) was observed at 3-year FUP, and 92.8% (77/83) at 5-year FUP. None of the aneurysms bled after treatment. During FUP, 6/83 patients (7.2%) were re-treated for residual aneurysm. Morbidity and mortality rates closely related to aneurysm occlusion were 0% (0/104).

CONCLUSION:

The WEB device was safe and effective for treating unruptured WIBAs, both in short-term and long-term FUPs.