bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a complex vocational rehabilitation intervention for patients with inflammatory arthritis: the WORK-ON study
Authors: Madsen Christina Merete Tvede , Primdahl Jette , Bremander Ann , Eggen Linda , Christensen Jeanette Reffstrup
Published: July 2023

Background

People with inflammatory arthritis often experience challenges at work and balancing paid work and energy in everyday life. Low work ability is common, and people with inflammatory arthritis face high risks of losing their jobs and permanent exclusion from the labour market. Context-specific tailored rehabilitation targeting persons with inflammatory arthritis is limited. The aim of this study is to describe the development of WORK-ON – a vocational rehabilitation for people with inflammatory arthritis.

Methods

Following the Medical Research Council’s framework for complex interventions, WORK-ON was developed based on existing evidence, interviews with patients and rehabilitation clinicians, a workshop, and an iterative process.

Results

The six-month vocational rehabilitation, WORK-ON, consists of 1) an initial assessment and goal setting by an occupational therapist experienced in rheumatology rehabilitation, 2) coordination by the same occupational therapist and individual support, including navigating across the primary and secondary health sectors, as well as social care, 3) group sessions for peer support, and 4) optionally individually tailored consultations with physiotherapists, nurses, or social workers.

Conclusion

WORK-ON is ready to be tested in a feasibility study.

Trial registration

The Regional Committees on Health Ethics for Southern Denmark stated that no formal ethical approval was necessary in this study (20,192,000–105).
Evaluation of the proper use of medication available over the counter by subsistence and emerging farmers in Mbombela Municipality, South Africa
Authors: Gulwako M. S. , Mokoele J. M. , Ngoshe Y. B. , Naidoo V.
Published: July 2023

South Africa has two types of animal farming systems, being the commercial industry and subsistence farming in more rural areas, with commercial farmers having more access to veterinary services. To cater for the absence of sufficient veterinary service, the country allows farmers to access certain over the counter medications (stock remedies), as a way to assist them to farm sustainably and profitably. However, with any drug use, their true benefits are only realized following correct use. The aim of this study was to describe and assess the adequacy of the current use of veterinary drugs by rural-based farmers. A scheduled structured questionnaire with close-ended questions and direct observation was employed. The most important finding was the absence of proper training in the area, with 82.9% not receiving any training related to livestock production or use/handling of stock remedies, highlighting the urgent need for proper training. Of interest, a large proportion of the farmers (57.5%) left the care of their animals to herders. Concerns were also noted in the application of withholding periods, transport of medication, disposal of medication, calculation of drug doses, correct route of administration and carcass disposal with no difference in response between farmers receiving training and those who didn’t. These finding not only indicates the importance of farmer training, but shows that for such training to be effective, information should not only cover farming activities but must include primary animal health care and an understanding of information contained in package leaflets. It would also be important to ensure that herdsmen are also included in such training initiatives as they are the primary careers of the animals.
Heme oxygenase 1 alleviates nonalcoholic steatohepatitis by suppressing hepatic ferroptosis
Authors: Yuan Xiwei , Li Lu , Zhang Ying , Ai Rong , Li Dongdong , Dou Yao , Hou Mengmeng , Zhao Dandan , Zhao Suxian , Nan Yuemin
Published: July 2023

Background

Heme oxygenase 1 (HO-1) has an influential but insufficiently investigated effect on ferroptosis, which is a novel form of programmed cell death and may play an effect on nonalcoholic steatohepatitis (NASH). However, the understanding of the mechanism is limited. Herein, our study aimed to explore the mechanism and role of HO-1 in NASH ferroptosis.

Methods

Hepatocyte conditional HO-1 knockout (HO-1HEPKO) C57BL/6J mice were established and fed a high-fat diet (HFD). Additionally, wild-type mice were fed either a normal diet or a HFD. Hepatic steatosis, inflammation, fibrosis, lipid peroxidation, and iron overload were assessed. AML12 and HepG2 cells were used to investigate the underlying mechanisms in vitro. Finally, liver sections from NASH patients were used to clinically validate the histopathology of ferroptosis.

Results

In mice, HFD caused lipid accumulation, inflammation, fibrosis, and lipid peroxidation, which were aggravated by HO-1HEPKO. In line with the in vivo results, HO-1 knockdown upregulated reactive oxygen species accumulation, lipid peroxidation, and iron overload in AML12 and HepG2 cells. Additionally, HO-1 knockdown reduced the GSH and SOD levels, which was in contrast to HO-1 overexpression in vitro. Furthermore, the present study revealed that the NF-κB signaling pathway was associated with ferroptosis in NASH models. Likewise, these findings were consistent with the liver histopathology results of NASH patients.

Conclusion

The current study showed that HO-1 could alleviate NASH progression by mediating ferroptosis.
Predictive value of monocyte to high-density lipoprotein cholesterol ratio and tumor markers in colorectal cancer and their relationship with clinicopathological characteristics
Authors: Zhang Xuan , Qin Hongyan , Tan Xiaodan , Mo Yuncong , Li Zhenyong , Huang Guofeng , Wei Zhixiao
Published: July 2023

Objective

To evaluate the predictive value of monocyte (M) to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) and tumor markers in colorectal cancer (CRC) and their correlation with clinicopathological characteristics.

Methods

Hematology test data and medical records of 202 CRC patients and 201 healthy subjects were collected retrospectively. The diagnostic efficacy of MHR was evaluated using receiver operating characteristic (ROC) curves and risk factors for CRC were analyzed by multivariate logistic regression.

Results

CRC patients had significantly higher M, MHR, carcinoembryonic antigen (CEA), and carbohydrate antigen 199 (CA199) levels, but significantly lower HDL-C levels than healthy controls (all P < 0.05). Additionally, MHR was positively correlated with tumor differentiation in CRC patients (P = 0.049); CEA and CA199 levels in CRC patients increased with increased stage, lymph node metastasis and tumor size ≥ 5 cm (all P < 0.05). Furthermore, high levels of MHR, CA199 and CEA were independent risk factors for CRC. The area under ROC curve of MHR combined with CEA and CA199 was 0.882/0.869 for the diagnosis of CRC, respectively.

Conclusion

This is the first study to explore the predictive value of MHR in CRC, and its continuous increase is an independent risk factor for CRC. MHR is a promising predictor for CRC progression along with CA199 and CEA.
Salivary microbiome and hypertension in the Qatari population
Authors: Murugesan Selvasankar , Al Khodor Souhaila
Published: July 2023

Background

The prevalence of hypertension in Qatar is 33 percent of the adult population. It is postulated that the salivary microbiome can regulate blood pressure (BP). However, limited investigations exist to prove this hypothesis. Therefore, we examined the difference in the salivary microbiome composition between hypertensive and normotensive Qatari subjects.

Methods

A total of 1190 Qatar Genome Project (QGP) participants (Mean age = 43 years) were included in this study. BP for all participants was classified into Normal (n = 357), Stage1 (n = 336), and Stage2: (n = 161) according to the American Heart Association guidelines. 16S-rRNA libraries were sequenced and analyzed using QIIME-pipeline, and PICRUST was used to predict functional metabolic routes. Machine Learning (ML) strategies were applied to identify salivary microbiome-based predictors of hypertension.

Results

Differential abundant analysis (DAA) revealed thatBacteroidesand Atopobiumwere the significant members of the hypertensive groups. Alpha and beta diversity indices indicated dysbiosis between the normotensive and hypertensive groups. ML-based prediction models revealed that these markers could predict hypertension with an AUC (Area under the curve) of 0.89. Functional predictive analysis disclosed that Cysteine and Methionine metabolism and the sulphur metabolic pathways involving the renin-angiotensin system were significantly higher in the normotensive group. Therefore, members ofBacteroidesandAtopobiumcan serve as predictors of hypertension. Likewise,Prevotella,Neisseria,andHaemophiluscan be the protectors that regulate BP via nitric acid synthesis and regulation of the renin-angiotensin system.

Conclusion

It is one of the first studies to assess salivary microbiome and hypertension as disease models in a large cohort of the Qatari population. Further research is needed to confirm these findings and validate the mechanisms involved.
Targeting macrophagic PIM-1 alleviates osteoarthritis by inhibiting NLRP3 inflammasome activation via suppressing mitochondrial ROS/Cl− efflux signaling pathway
Authors: Zhang Zhen , Xie Shujun , Qian Jin , Gao Fengqiang , Jin Wenjian , Wang Lingqiao , Yan Lili , Chen Hao , Yao Wangxiang , Li Maoqiang , Wang Xuepeng , Zhu Liulong
Published: July 2023

Background

Osteoarthritis (OA), in which macrophage-driven synovitis is considered closely related to cartilage destruction and could occur at any stage, is an inflammatory arthritis. However, there are no effective targets to cure the progression of OA. The NOD-, LRR-,and pyrin domain-containing protein 3 (NLRP3) inflammasome in synovial macrophages participates in the pathological inflammatory process and treatment strategies targeting it are considered to be an effective approach for OA. PIM-1 kinase, as a downstream effector of many cytokine signaling pathways, plays a pro-inflammatory role in inflammatory disease.

Methods

In this study, we evaluated the expression of the PIM-1 and the infiltration of synovial macrophages in the human OA synovium. The effects and mechanism of PIM-1 were investigated in mice and human macrophages stimulated by lipopolysaccharide (LPS) and different agonists such as nigericin, ATP, Monosodium urate (MSU), and Aluminum salt (Alum). The protective effects on chondrocytes were assessed by a modified co-culture system induced by macrophage condition medium (CM). The therapeutic effect in vivo was confirmed by the medial meniscus (DMM)-induced OA in mice.

Results

The expression of PIM-1 was increased in the human OA synovium which was accompanied by the infiltration of synovial macrophages. In vitro experiments, suppression of PIM-1 by SMI-4a, a specific inhibitor, rapidly inhibited the NLRP3 inflammasome activation in mice and human macrophages and gasdermin-D (GSDME)-mediated pyroptosis. Furthermore, PIM-1 inhibition specifically blocked the apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization in the assembly stage. Mechanistically, PIM-1 inhibition alleviated the mitochondrial reactive oxygen species (ROS)/chloride intracellular channel proteins (CLICs)-dependent Cl− efflux signaling pathway, which eventually resulted in the blockade of the ASC oligomerization and NLRP3 inflammasome activation. Furthermore, PIM-1 suppression showed chondroprotective effects in the modified co-culture system. Finally, SMI-4a significantly suppressed the expression of PIM-1 in the synovium and reduced the synovitis scores and the Osteoarthritis Research Society International (OARSI) score in the DMM-induced OA model.

Conclusions

Therefore, PIM-1 represented a new class of promising targets as a treatment of OA to target these mechanisms in macrophages and widened the road to therapeutic strategies for OA.
A national assessment of urban forest carbon storage and sequestration in Canada
Authors: Steenberg James W. N. , Ristow Melissa , Duinker Peter N. , Lapointe-Elmrabti Lyna , MacDonald J. Douglas , Nowak David J. , Pasher Jon , Flemming Corey , Samson Cameron
Published: July 2023

During a time of rapid urban growth and development, it is becoming ever more important to monitor the carbon fluxes of our cities. Unlike Canada’s commercially managed forests that have a long history of inventory and modelling tools, there is both a lack of coordinated data and considerable uncertainty on assessment procedures for urban forest carbon. Nonetheless, independent studies have been carried out across Canada. To improve upon Canada’s federal government reporting on carbon storage and sequestration by urban forests, this study builds on existing data to develop an updated assessment of carbon storage and sequestration for Canada’s urban forests. Using canopy cover estimates derived from ortho-imagery and satellite imagery ranging from 2008 to 2012 and field-based urban forest inventory and assessment data from 16 Canadian cities and one US city, this study found that Canadian urban forests store approximately 27,297.8 kt C (− 37%, + 45%) in above and belowground biomass and sequester approximately 1497.7 kt C year−1 (− 26%, + 28%). In comparison with the previous national assessment of urban forest carbon, this study suggested that in urban areas carbon storage has been overestimated and carbon sequestration has been underestimated. Maximizing urban forest carbon sinks will contribute to Canada’s mitigation efforts and, while being a smaller carbon sink compared to commercial forests, will also provide important ecosystem services and co-benefits to approximately 83% of Canadian people.
A phase 1/2 study of azacitidine, venetoclax and pevonedistat in newly diagnosed secondary AML and in MDS or CMML after failure of hypomethylating agents
Authors: Short Nicholas J. , Muftuoglu Muharrem , Ong Faustine , Nasr Lewis , Macaron Walid , Montalban-Bravo Guillermo , Alvarado Yesid , Basyal Mahesh , Daver Naval , Dinardo Courtney D. , Borthakur Gautam , Jain Nitin , Ohanian Maro , Jabbour Elias , Issa Ghayas C. , Qiao Wei , Huang Xuelin , Kanagal-Shamanna Rashmi , Patel Keyur P. , Bose Prithviraj , Ravandi Farhad , Delumpa Ricardo , Abramova Regina , Garcia-Manero Guillermo , Andreeff Michael , Cortes Jorge , Kantarjian Hagop
Published: July 2023

Background

Pevonedistat is a first-in-class, small molecular inhibitor of NEDD8-activating enzyme that has clinical activity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Preclinical data suggest synergy of pevonedistat with azacitidine and venetoclax.

Methods

This single-center, phase 1/2 study evaluated the combination of azacitidine, venetoclax and pevonedistat in older adults with newly diagnosed secondary AML or with MDS or chronic myelomonocytic leukemia (CMML) after failure of hypomethylating agents. Patients received azacitidine 75 mg/m2 IV on days 1–7, venetoclax at maximum dose of 200-400 mg orally on days 1–21 (AML cohort) or days 1–14 (MDS/CMML cohort) and pevonedistat 20 mg/m2 IV on days 1, 3 and 5 for up to 24 cycles. The primary endpoints for the phase 2 portion of the study were the CR/CRi rate in the AML cohort and the overall response rate (CR + mCR + PR + HI) in the MDS/CMML cohort.

Findings

Forty patients were enrolled (32 with AML and 8 with MDS/CMML). In the AML cohort, the median age was 74 years (range 61–86 years), and 27 patients (84%) had at least one adverse risk cyto-molecular feature, including 15 (47%) with a TP53 mutation or MECOM rearrangement; seventeen patients (53%) had received prior therapy for a preceding myeloid disorder. The CR/CRi rate was 66% (CR 50%; CRi 16%), and the median overall survival (OS) was 8.1 months. In the MDS/CMML cohort, 7 patients (87%) were high or very high risk by the IPSS-R. The overall response rate was 75% (CR 13%; mCR with or without HI 50%; HI 13%). The most common grade 3–4 adverse events were infection in 16 patients (35%), febrile neutropenia in 10 patients (25%) and hypophosphatemia in 9 patients (23%). In an exploratory analysis, early upregulation of NOXA expression was observed, with subsequent decrease in MCL-1 and FLIP, findings consistent with preclinical mechanistic studies of pevonedistat. Upregulation of CD36 was observed, which may have contributed to therapeutic resistance.

Conclusions

The triplet combination of azacitidine, venetoclax and pevonedistat shows encouraging activity in this very poor-risk population of patients with AML, MDS or CMML.

Trial registration ClinicalTrials.gov (NCT03862157).
Acetylcysteine and budesonide for the treatment of refractory Mycoplasma pneumoniae pneumonia in children: a clinical observation
Authors: Wang Yanli , Liu Kai , Chen Chuangui , Zhang Chengyun
Published: July 2023

Background

To examine the clinical impact of bronchoscope alveolar lavage (BAL) combination with budesonide, ambroxol + budesonide, or acetylcysteine + budesonide in the treatment of refractory Mycoplasma pneumoniae pneumonia (RMPP).

Methods

Eighty-two RMPP patients admitted to Pediatrics at The First People’s Hospital of Zhengzhou were retrospectively evaluated between August 2016 and August 2019. All patients were administered BAL in addition to intravenous Azithromycin, expectoration, and nebulizer inhalation. The medications added to the BLA separated the patients into the Budesonide group, Ambroxol + budesonide group, and acetylcysteine + budesonide group. Analyzed were the variations in laboratory examination indices, improvement in lung imaging, overall effective rate, and adverse responses in the three groups.

Results

The laboratory test indices of patients in all three groups improved significantly relative to pre-treatment levels, and the results were statistically significant. After therapy, there were no significant differences between the three groups in terms of white blood cell (WBC), C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR). Serum lactate dehydrogenase (LDH) and serum ferritin (SF) varied significantly across the three groups (P < 0.05). In the acetylcysteine + budesonide group, the absorption rate of lung imaging lesions and clinical efficacy were superior to those of the other two groups. There were no significant differences between the three groups in the occurrence of adverse events (P > 0.05).

Conclusions

BLA-coupled acetylcysteine + budesonide was superior to the other two groups in enhancing the effectiveness of RMPP in children, which might increase lung opacity absorption and minimize lung inflammation.
Effects of low-dose intravenous heparin therapy in aneurysmal subarachnoid hemorrhage: a randomized controlled clinical trial protocol
Authors: Zhang Yifan , Hu Jiangang
Published: July 2023

Background

Heparin anticoagulation therapy is a widely used method to prevent cerebral vasospasm (CV) and venous thrombosis in patients with subarachnoid hemorrhage caused by ruptured cerebral aneurysms. Subcutaneous heparin injection is considered safe and effective, whereas continuous intravenous heparin infusion is still being debated due to the risk of bleeding. Although most retrospective studies have confirmed the safety and effectiveness of unfractionated heparin (UFH) after aneurysm embolization therapy and its ability to reduce CV, there is still no randomized clinical trial comparing UFH and subcutaneous low-molecular-weight heparin (LMWH) injection in this population. Therefore, this study aims to compare the clinical outcomes associated with these two treatment approaches.

Methods

The study is an open-label, single-center, randomized controlled trial and aims to recruit 456 patients, with 228 patients in each group. The primary outcome was CV; the second outcomes measures are occurrence of bleeding events, ischemic events, heparin-induced thrombocytopenia, deep vein thrombosis, cerebral venous circulation time, brain edema score, and hydrocephalus incidence.

Ethics and dissemination

This study protocol obtained ethical approval from the Ethics Committee of Baoan People’s Hospital, Shenzhen, Guangdong (approval number: BYL20220805). This work will be published in peer-reviewed international medical journals and presented at medical conferences.

Trial registration

ClinicalTrials ID: NCT05696639. Registered on March 30, 2023.
Learnings from clinical trials in patients with connective tissue disease-associated interstitial lung disease
Authors: Higuero Sevilla Jean Paul , Memon Areeka , Hinchcliff Monique
Published: July 2023

Many clinical trial results are available to inform best practices in the treatment of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD).

Herein, we summarize the results of clinical trials, including patient-reported outcome instruments, for the treatment of patients with ILD associated with systemic sclerosis (SSc/scleroderma), rheumatoid arthritis, and idiopathic inflammatory myositis, the diseases with the most available data. For SSc-ILD, the US Food and Drug Administration approved nintedanib (a tyrosine kinase inhibitor) in 2020 and subcutaneous tocilizumab (an IL-6 receptor monoclonal antibody) in 2021. Rituximab was recently shown to have similar efficacy but better tolerability than intravenous cyclophosphamide (CYC) for CTD-ILD therapy. Scleroderma Lung Study II, conducted in patients with SSc-ILD, showed that oral CYC and mycophenolate mofetil (MMF) were comparable in their effects on lung function, but MMF was better tolerated. The increasing treatment armamentarium for patients with CTD-ILD offers physicians new opportunities to improve patient outcomes.
The access route through the anatomical snuffbox in ultrasound-guided synovial biopsy of the wrist allows for a safe and effective collection of tissue samples in inflammatory arthritis
Authors: De Stefano Ludovico , Bugatti Serena , Piccin Veronica , D’Ambrosio Gioacchino , Luvaro Terenzj , Xoxi Blerina , Montecucco Carlomaurizio , Manzo Antonio
Published: July 2023

Background

A proof-of-concept study to evaluate the feasibility and safety of minimally invasive ultrasound (US)-guided synovial biopsy of the radiocarpal (RC) joint using the anatomical snuffbox as an access route.

Methods

Twenty consecutive patients with active chronic arthritis of the wrist underwent minimally invasive US-guided synovial biopsy of the RC joint using the anatomical snuffbox as the access route. Samples were retrieved from 3 predetermined biopsy target sites of the RC synovia (proximal, vault, and distal site), aiming for a minimum of 12 samples. The procedure’s feasibility was evaluated based on the number and histological quality of retrieved tissue fragments tested on pre-defined histometric parameters. The safety and tolerability of the procedure were assessed through 1-week and 1-month follow-up clinical evaluations.

Results

A median number of 17 fragments (≥ 1 mm diameter size at macroscopic evaluation) per procedure was processed for histopathology (range 9–24) and dedicated to the study. At the histopathologic evaluation, a gradable tissue (visible lining layer and ≥ 4 fragments with IST) was recognized in 19/20 biopsies (95%), and all pre-defined histometric parameters were judged applicable and successfully measured in 19/19 gradable biopsies. All three biopsy target sites showed sampling accessibility. The entire procedure was generally well tolerated. At the 1-month follow-up, no patients showed infectious complications.

Conclusions

The access route through the anatomical snuff box in US-guided synovial biopsies of the RC joint allows for a safe and targeted collection of adequate tissue samples. This modification of the traditional access route may allow easier, repeatable, and safer sampling of anatomically distinct areas of the wrist in the course of arthritis.
Horizontal jump asymmetries are associated with reduced range of motion and vertical jump performance in female soccer players
Authors: Roso-Moliner Alberto , Lozano Demetrio , Nobari Hadi , Bishop Chris , Carton-Llorente Antonio , Mainer-Pardos Elena
Published: July 2023

Background

Performance in jumping and change of direction tests are good proxies to reflect the skill level during soccer-specific actions. Greater inter-leg asymmetries have been identified as a risk factor for developing acute and overuse injuries and jeopardizing soccer performance. The aim of this study was to assess the association between asymmetry in the unilateral vertical and horizontal jump tests, ankle range of motion, linear velocity, and change of direction in a sample of highly trained adult female soccer players.

Methods

Thirty-eight highly trained female soccer players underwent a testing protocol including ankle dorsiflexion, single leg jumps for height (CMJ), distance (HJ), 40 m sprint and 180° change of direction tests.

Results

Within-session reliability was acceptable (CV ≤ 7.9%), and relative reliability showed good to excellent (ICC: 0.83 to 0.99). The one-way ANOVA reported higher inter-limb differences for change of direction deficit (10.9 ± 8.04%) and single leg CMJ (5.70 ± 5.22%). Pearson correlations highlighted significant relationships between horizontal jump asymmetries and ankle dorsiflexion (r = -0.41), CMJ (r = -0.36 to -0.49) and HJ (r = -0.28 to -0.56).

Conclusions

Assessing inter-limb asymmetries through different methods can help scientists understand the specificity of their detrimental effects on soccer performance. Practitioners should be aware of these specificities as well as the magnitude and direction of the asymmetries when aiming to improve specific on-field skills.
Gut microbiota-derived tryptophan metabolites alleviate liver injury via AhR/Nrf2 activation in pyrrolizidine alkaloids-induced sinusoidal obstruction syndrome
Authors: Shang Haitao , Huang Chao , Xiao Zhuanglong , Yang Pengcheng , Zhang Shengyan , Hou Xiaohua , Zhang Lei
Published: July 2023

Background and aims

Hepatic sinusoidal obstruction syndrome (HSOS) is caused by toxic injury, such as pyrrolizidine alkaloids, to the liver sinusoidal endothelial cells, and the gut microbiota may be involved. However, the specific role and underlying mechanism of gut microbiota in HSOS is unknown.

Methods

HSOS model was established by gavage of monocrotaline (MCT) in rats. Fecal microbiota transplantation (FMT) with HSOS-derived or healthy gut flora was also conducted to validate the role of gut microflora in MCT-induced liver injury. The microbial 16 s rRNA analysis and untargeted metabolomics analysis in the faeces were performed to identify HSOS-related flora and metabolites. Finally, by supplementation with specific tryptophan metabolites, such as indole-3-acetaldehyde (IAAld) and indole acetic acid (IAA), we further confirmed the role of tryptophan metabolism in HSOS and the role of the AhR/Nrf2 pathway in MCT-induced liver injury.

Results

MCT induced HSOS-like liver injury in rats with significantly altered gut microbiota. Particularly, some tryptophan-metabolizing bacteria reduced in MCT-treated rats, such as Bacteroides, Bifidobacterium, Lactobacillus and Clostridium, and accompanied by a decrease in microbial tryptophan metabolic activity and a series of tryptophan derivatives. Restoring the gut microbiota via FMT improved MCT-induced liver damage, while HSOS-derived gut microbiota aggravated the liver injury induced by MCT. Supplementation with microbial tryptophan derivatives (IAAld or IAA), or 6-formylindolo(3,2-b)carbazole (Ficz, an AhR agonist) could activate the AhR/Nrf2 signaling pathway, thereby attenuating the MCT-induced liver oxidative stress and liver sinusoidal endothelial cells injury.

Conclusions

Gut microbiota plays a critical role in MCT-induced HSOS, with inadequate microbial tryptophan metabolism in the gut and consequently a lower activity of the AhR/Nrf2 signaling pathway in the liver, which should be a potential target for the management of HSOS.
Intermittent body composition analysis as monitoring tool for muscle wasting in critically ill COVID-19 patients
Authors: Kolck Johannes , Rako Zvonimir A. , Beetz Nick L. , Auer Timo A. , Segger Laura K. , Pille Christian , Penzkofer Tobias , Fehrenbach Uli , Geisel Dominik
Published: July 2023

Objectives

SARS-CoV-2 virus infection can lead to acute respiratory distress syndrome (ARDS), which can be complicated by severe muscle wasting. Until now, data on muscle loss of critically ill COVID-19 patients are limited, while computed tomography (CT) scans for clinical follow-up are available. We sought to investigate the parameters of muscle wasting in these patients by being the first to test the clinical application of body composition analysis (BCA) as an intermittent monitoring tool.

Materials

BCA was conducted on 54 patients, with a minimum of three measurements taken during hospitalization, totaling 239 assessments. Changes in psoas- (PMA) and total abdominal muscle area (TAMA) were assessed by linear mixed model analysis. PMA was calculated as relative muscle loss per day for the entire monitoring period, as well as for the interval between each consecutive scan. Cox regression was applied to analyze associations with survival. Receiver operating characteristic (ROC) analysis and Youden index were used to define a decay cut-off.

Results

Intermittent BCA revealed significantly higher long-term PMA loss rates of 2.62% (vs. 1.16%, p < 0.001) and maximum muscle decay of 5.48% (vs. 3.66%, p = 0.039) per day in non-survivors. The first available decay rate did not significantly differ between survival groups but showed significant associations with survival in Cox regression (p = 0.011). In ROC analysis, PMA loss averaged over the stay had the greatest discriminatory power (AUC = 0.777) for survival. A long-term PMA decline per day of 1.84% was defined as a threshold; muscle loss beyond this cut-off proved to be a significant BCA-derived predictor of mortality.

Conclusion

Muscle wasting in critically ill COVID-19 patients is severe and correlates with survival. Intermittent BCA derived from clinically indicated CT scans proved to be a valuable monitoring tool, which allows identification of individuals at risk for adverse outcomes and has great potential to support critical care decision-making.
The relationship between aspirin consumption and hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Wang Shuai , Zuo Lijuan , Lin Zhaojin , Yang Zhiqin , Chen Ran , Xu Yan
Published: July 2023

Background

Recent studies have shown that aspirin consumption may reduce the risk of hepatocellular carcinoma (HCC), but their correlation is still not fully understood. This meta-analysis aimed to investigate the correlation between aspirin consumption and HCC.

Methods

A systematic literature search was conducted on PubMed, Scopus, Cochrane Library, EMBASE, and Web of Science databases. The search period was from the establishment of the database to July 1, 2022 with no language restrictions.

Results

A total of 19 studies including three prospective studies and 16 retrospective ones with 2,217,712 patients were included. Compared with those who did not take aspirin, those who took aspirin had a 30% lower risk of HCC (hazard ratio [HR] = 0.70, 95% confidence interval [CI] 0.63–0.76,I2 = 84.7%,P < 0.001). Subgroup analysis showed that aspirin significantly reduced the risk of HCC by 19% in Asia (HR = 0.81, 95% CI 0.80–0.82,I2 = 85.2%,P < 0.001) and by 33% (HR = 0.67, 95% CI 0.61–0.73,I2 = 43.6%,P = 0.150) in Europe and the U.S with no significant difference. Moreover, in patients with HBV or HCV infection, aspirin reduced 19% and 24% of the risk of HCC, respectively. However, aspirin administration might increase risks of gastrointestinal bleeding in patients with chronic liver disease (HR = 1.14, 95% CI 0.99–1.31,I2 = 0.0%,P = 0.712). Sensitivity analysis showed no significant difference of results after excluding individual studies, suggesting that the results were robust.

Conclusion

Aspirin may reduce the risk of HCC in both healthy population and patients with chronic liver disease. However, attention should be paid to adverse events such as gastrointestinal bleeding in patients with chronic liver disease.
Adenosine, Lidocaine and Magnesium (ALM) therapy modulates early sex-specific inflammatory and immune responses following experimental anterior cruciate ligament rupture and reconstruction
Authors: Morris Jodie L. , McEwen Peter C. , Letson Hayley L. , Dobson Geoffrey P.
Published: July 2023

Background

Early dysregulation of local and systemic inflammatory and immune responses is implicated in the pathogenesis of fibrotic and degenerative complications after anterior cruciate ligament reconstruction (ACLR) surgery. In other surgical trauma models, ALM therapy has been shown to blunt inflammation, leading to a more permissive healing environment in injured tissues. The purpose of this study was to evaluate sex-specific effects of surgery and perioperative ALM therapy on leukocyte mobilization and activation, and systemic and joint tissue inflammation in a rat model of ACL rupture and reconstruction.

Methods

Adult male and female Sprague–Dawley rats were randomly divided into ALM (male, n = 15; female, n = 14) or Saline control (male, n = 13; female, n = 14) treatment groups. Three days after non-invasive ACL rupture, ACLR surgery was performed on the injured knee. Animals received a 1 h perioperative IV ALM or saline drip, and a 0.1 ml IA bolus of ALM or saline, and were monitored to 120 h postoperative. Hematology, leukocyte immunophenotyping, plasma and synovial inflammatory mediator concentrations, and joint tissue histopathology and gene expression of inflammatory markers were assessed.

Results

Following ACLR surgery, plasma concentrations of inflammatory cytokines IL-6, TNF-α and IL-1β peaked later and at a higher magnitude in females compared to males, with ALM dampening this systemic inflammatory response. At 1 h postoperative, ALM boosted circulating B cell numbers in males and females, and decreased neutrophil activation in females. By 72 h, numbers of circulating T cells with immunoregulatory potential were increased in all ALM-treated animals compared to Saline controls, and corresponded to a significant reduction in synovial TNF-α concentrations within the operated knees. Sex-specific treatment differences were found in inflammatory and immune profiles in the synovial fluid and joint tissues. Inflammatory cell infiltration and gene expression of markers of inflammation (Nfκb, Nlrp3), cytoprotective responses (Nrf2), and angiogenesis (Vegf) were increased in joint synovial tissue from ALM-treated males, compared to controls. In females, ALM treatment was associated with increased mononuclear cell recruitment, and expression of M2 macrophage marker (Arg1) in joint synovial tissue.

Conclusions

ALM has differential effects on the immuno-inflammatory response of males and females in the early postoperative period after ACLR surgery, with potential implications for subsequent joint tissue repair processes.
Gene polymorphism of FTO rs8050136 and CDKAL1 rs10946398 and their association with type 2 diabetes mellitus in the Egyptian patients
Authors: Ragab Halla M. , El Maksoud Nabila Abd , Amin Mona A. , Elaziz Wafaa Abd
Published: July 2023

Background

An extensive quest for genetic variables impacting the susceptibility for type 2 diabetes mellitus (T2DM) and other cardiometabolic disorders has been sparked by the global growth in the frequency of those widespread ailments. Although the association between several SNPs and T2DM has been reported in prior research, little is known about the association between SNPs FTO rs8050136, and CDKAL1 rs10946398 and T2DM in Egyptian population. This study aims to investigate these two identified SNPs in Egyptian diabetic patients to ascertain their underlying genetic influences on T2DM. This study included 50 diabetic patients and 50 healthy subjects. Each individual underwent a clinical assessment and total body examination, laboratory investigations including liver enzymes, fasting blood sugar, glycated hemoglobin (HbA1C), and lipid profile. The DNA Purification Kit was used to separate genomic DNA from the whole blood. Gene polymorphism was detected via PCR-REFLP and PCR-AS methods.

Results

There was a significant association between the presence of the C allele in the FTO gene at rs8050136 and T2DM among studied people. The patient group had a considerably higher frequency of the FTO "AC" genotype and the "C" allele (P < 0.05). Additionally, only the wild-type homozygous “GG” of the CDKAL1 rs10946398 was found in all the studied cases.

Conclusions

The FTO "CC" genotype is significantly associated with T2DM in the Egyptian population. However, no association was detected between CDKAL1 rs10946398 and T2DM. This result may be attributed to the small sample size or the rare incidence of this SNP in the Egyptian population. The study suggests verifying the findings on a larger sample and looking into the relationship between T2DM and additional gene polymorphisms.
Isolation and evaluation of erythroid progenitors in the livers of larval, froglet, and adult Xenopus tropicalis
Authors: Omata Kazuki , Nomura Ikki , Hirata Akito , Yonezuka Yuka , Muto Hiroshi , Kuriki Ryo , Jimbo Kirin , Ogasa Koujin , Kato Takashi
Published: July 2023

Xenopus liver maintains erythropoietic activity from the larval to the adult stage. During metamorphosis, thyroid hormone mediates apoptosis of larval-type erythroid progenitors and proliferation of adult-type erythroid progenitors, and a globin switch occurs during this time. In addition, the whole-body mass and the liver also change; however, whether there is a change in the absolute number of erythroid progenitors is unclear. To isolate and evaluate erythroid progenitors in the Xenopus liver, we developed monoclonal ER9 antibodies against the erythropoietin receptor (EPOR) of Xenopus. ER9 recognized erythrocytes, but not white blood cells or thrombocytes. The specificity of ER9 for EPOR manifested as its inhibitory effect on the proliferation of a Xenopus EPOR-expressing cell line. Furthermore, ER9 recognition was consistent with epor gene expression. ER9 staining with Acridine orange (AO) allowed erythrocyte fractionation through fluorescence-activated cell sorting. The ER9+ and AO-red (AOr)high fractions were highly enriched in erythroid progenitors and primarily localized to the liver. The method developed using ER9 and AO was also applied to larvae and froglets with different progenitor populations from adult frogs. The liver to body weight and the number of ER9+ AOrhigh cells per unit body weight were significantly higher in adults than in larvae and froglets, and the number of ER9+ AOrhigh cells per unit liver weight was the highest in froglets. Collectively, our results show increased erythropoiesis in the froglet liver and demonstrate growth-dependent changes in erythropoiesis patterns in specific organs of Xenopus.
A CIDADANIA E A POLÍTICA PEDAGÓGICA
Authors: Silva Mello Josué
Published: July 2023

A questão da cidadania, e deu seu pleno exercício, emerge como um tema da maior relevância para a sociedade e para o processo educativo. Para a sociedade, porquanto da consciência e do exercício da cidadania dependem a efetivação e consolidação da democracia, como forma de vida e de busca permanente de transformação da organização social, na conquista de sua realização histórica. Relevante para a educação, na medida em que lhe é atribuído o papel, na dimensão de objetivo maior, de preparar indivíduos para o exercício consciente da cidadania. Neste texto, pretende-se apresentar uma síntese da pesquisa realizada em escolas públicas de Feira de Santana, sistematizada na Dissertação de Mestrado em Educação, apresentada à Universidade Federal da Bahia, tendo como objeto a compreensão da relação entre educação e cidadania, especificamente, a forma como a questão da cidadania vem sendo vivenciada e trabalhada na prática pedagógica da escola básica. Busca-se, antes, investigar a concepção de cidadania, construída no curso da história, no contexto da sociedade liberal democrática, partindo-se, evidentemente, da cultura clássica greco-romana, analisando-se, em seguida, a relação entre cidadania e educação, entre cidadania e a prática vivenciada em escolas públicas de 1º grau.
CRIAÇÃO LITERÁRIA
Authors: Das Virgens Aldo , Aureo Augusto  , Borges Crisanto , Rodrigues Henrique , Figueiredo Herivelton , Hermes José , D'Eça Manoel , Carneiro Miguel , Lopes Raymundo Luiz
Published: July 2023

Tritura um pedregulho de rimase engole a fábulada indigestãonasce o verso

Godofredo Filho
LÓGICA CLÁSSICA: UM PROBLEMA DE IDENTIDADE
Authors: Moreira Tenório Robinson
Published: July 2023

O princípio da identidade afirma que tudo é idêntico a si mesmo. Por trás da obviedade aparente do princípio da identidade, e no âmbito da lógica clássica, jazem dois outros princípios, o princípio da não-contradição e o princípio do terceiro-excluído, cuja universalidade está longe de ser unanimemente considerada.
PROBLEMAS FILOSÓFICOS DO CONHECIMENTO MATEMÁTICO
Authors: Borges Carloman Carlos
Published: July 2023

Diversos problemas pertinentes à Filosofia da Matemática são aqui mencionados − seguidos de respostas parciais. Restringe-se este ensaio quase inteiramente à abordagem construtivista corrente, também, designada por alguns autores por intuicionismo, cujo líder máximo foi o matemático holandês L.E.J. BROUWER. A finalidade do artigo é abordar questões de um modo bem informal, a fim de que um número maior de pessoas sem treinamento técnico tenha acesso a elas.
O ENSINO DA ENFERMAGEM PSIQUIÁTRICA BASEADO NO RELACIONAMENTO TERAPÊUTICO - EXPERIÊNCIA PSICOSSOMÁTICA
Authors: Silva Maria da Luz , Nascimento Macedo Edna Lúcia
Published: July 2023

O ensino de Enfermagem Psiquiátrica tem suscitado muitos questionamentos e discussões, em decorrência da dificuldade de mensurar-se as ações do enfermeiro no âmbito da prática, muito embora o assistir em Enfermagem, nos dias atuais, implique a visão do homem como um todo, que sofre ao mesmo tempo transtornos físicos e psíquicos interligados e interdependentes. O cuidado de enfermagem, orientado para o atendimento integral, não pode deixar de valorizar a importância do relacionamento enfermeiro-paciente como instrumento imprescindível à atuação do Enfermeiro. O ensino da Enfermagem Psiquiátrica baseado no relacionamento terapêutico, como é abordado neste trabalho, prioriza o acompanhamento do aluno numa experiência de relacionamento interpessoal com o paciente, estimulando-o a lidar com seus sentimentos e preconceitos quer diante da prática, da vida e da profissão, tendo como suporte a Teoria de Peplau.
APLICAÇÃO DA METODOLOGIA SISTÊMICA AO ESTUDO DO SÍTIO URBANO DE FEIRA DE SANTANA - BA
Authors: Pacheco de Almeida José Antonio
Published: July 2023

A pesquisa foi desenvolvida com base na teoria geossistêmica, considerando o geossistema como uma unidade  de paisagem complexa, onde interagem elementos bióticos, abióticos e antrópicos. Dessa forma, o presente trabalho procurou, com base na compartimentação geomorfológica da área de estudo, definir os vários aspectos naturais da paisagem, identificar os conflitos ecológicos impactantes decorrentes do uso e ocupação do solo urbano, bem como, suas inter-relações e conseqüências  sobre a dinâmica natural.
ANÁLISE CONJUNTURAL DOS JUIZADOS ESPECIAIS DE PROTEÇÃO À MULHER E A DEMOCRATIZAÇÃO DO ACESSO À JUSTIÇA
Authors: Cássia Santos Carneiro Valnêda
Published: July 2023

Este artigo tem como temática analisar, conjunturalmente,a previsão legal dos Juizados Especiais de Proteção à Mulher enquantomecanismo de ampliação do acesso à Justiça pela população. A análisefoi, por essência, panorâmica, partindo das noções básicas da democraciapara a Ciência Política, perpassando pelas funções do Estado e doPoder Judiciário, para, ao final, apontar suas evoluções, com a criaçãodos Juizados Especiais Cíveis, pela Lei n. 9.099/95 e dos atuais JuizadosEspeciais de Proteção à Mulher, pela Lei n. 11.340/06. Conclui-se queo Estado Brasileiro tem evoluído no quesito democratização do acessoà Justiça, mas ainda se percebe que essa missão é alcançada numaassociação a clamores públicos, devendo o Governo assumir o papel deimplementar, progressivamente, novas políticas para garantir, não somenteo acesso ao Judiciário, mas, a efetividade de suas medidas.
METODOLOGIA PARA AVALIAÇÃO EX ANTE E EXPOST DA RELEVÂNCIA SOCIAL DE POLÍTICAS PÚBLICAS
Authors: Afonso Ferreira Maia José
Published: July 2023

Este artigo consiste em uma abordagem metodológica paraavaliar ex ante e ex post, políticas públicas, sob o enfoque social deeficiência. Busca estabelecer o elo entre o princípio da eficiência econômica,axiologicamente demonstrado, e a eficiência social, coerentecom o postulado de preferência e seus axiomas de transitividade e indiferença,que fundamentam a teoria econômica da escolha ótima, combase no método matricial e na inferência estatística. O autor apresentaos principais indicadores de avaliação ex post no campo da implementaçãoe gestão de programas, projetos, e ações finalísticas associados a macroobjetivose objetivos específicos, utilizando, a título de exemplo e noplano teórico, aqueles formulados no Plano de Desenvolvimento Econômicodo Estado Bahia: 2020, do ano de 2006, como critérios e subcritériosde avaliação e de hierarquização da relevância social ex ante e ex postdos programas e projetos e ações finalísticas a serem contemplados nessePlano.
FIDELIDADE: UMA NECESSIDADE DO ESTADO MODERNO
Authors: Viana de Souza Joselito
Published: July 2023

O presente artigo sugere uma administração pública contemporâneaque busque uma avaliação contínua dos conceitos e dasexperiências vividas. Essa administração deverá estar sintonizada coma constante do mercado, ou seja, deve ser uma administração capaz delidar com as mudanças que atendam aos anseios dos cidadãos/clientes.Sugere, também, que as políticas públicas deverão contemplar soluçõesàs insatisfações dos cidadãos/clientes em relação ao Estado, tornandoossatisfeitos e, conseqüentemente, fiéis.
DESENVOLVIMENTO SUSTENTÁVEL DE SISTEMAS DE PRODUÇÃO DE FRUTAS TROPICAIS NATIVAS E EXÓTICAS – ABORDAGEM MESOANALÍTICA
Authors: Lacerda Ramos Eduardo
Published: July 2023

Preocupamo-nos com uma abordagem teórica mesoanalíticacom a qual se possa esclarecer como o Sistema de Produção Agroindustrialde Frutas Tropicais Nativas e Exóticas venha a ter sucesso em termos dedesenvolvimento autosustentável e de longo prazo. Ponderando-se (emsimulação) o grau de influência de dezesseis Elementos do Sistema (consideradoscomo potencialmente de sucesso) sobre problemas (Desafios) enfrentadospelas Cadeias de Produção Agroindustrial do Umbu (Preservação Ambiental,Escala de Oferta, Escala de Demanda e Nível Tecnológico), concordousetentativamente que tecnologia é o fator de produção que em maiorpeso pode contribuir para o referido sucesso. Também exploramos aaplicação das diversas políticas costumeiramente consideradas no enfrentamentode problemas existentes nos diversos segmentos da cadeia de produção.Finalmente, apresentamos sugestões de como valorizar a tecnologia ouo ramo da ciência e da tecnologia na aglutinação de forças da sociedadeem prol do desenvolvimento do Sistema de Produção Agroindustrial deFrutas Tropicais Nativas e Exóticas.