bluuebunny/crossref_metadata_2025 huggingface dataset:
Dexmedetomidine alleviates pulmonary fibrosis through the ADORA2B-Mediated MAPK signaling pathway
Authors: Lai Xiaofan , Lin Yingying , Huang Shaojie , Pu Lvya , Zeng Qihao , Wang Zhongxing , Huang Wenqi
Published: August 2023

Background

Idiopathic pulmonary fibrosis (IPF) is a chronically progressive fibrotic pulmonary disease characterized by an uncertain etiology, a poor prognosis, and a paucity of efficacious treatment options. Dexmedetomidine (Dex), an anesthetic-sparing alpha-2 adrenoceptor (α2AR) agonist, plays a crucial role in organ injury and fibrosis. However, the underlying mechanisms of IPF remain unknown.

Methods

In our study, the role of Dex in murine pulmonary fibrosis models was determined by Dex injection intraperitoneally in vivo. Fibroblast activation and myofibroblast differentiation were assessed after Dex treatment in vitro. The activation of MAPK pathway and the expression of Adenosine A2B receptor (ADORA2B) were examined in lung myofibroblasts. Moreover, the role of ADORA2B in Dex suppressing myofibroblast differentiation and pulmonary fibrosis was determined using the ADORA2B agonist BAY60-6583.

Results

The results revealed that Dex could inhibit Bleo-induced pulmonary fibrosis in mice. In vitro studies revealed that Dex suppressed TGF-β-mediated MAPK pathway activation and myofibroblast differentiation. Furthermore, Dex inhibits myofibroblast differentiation and pulmonary fibrosis via downregulating ADORA2B expression.

Conclusions

Our findings suggest Dex as a potential therapeutic agent for pulmonary fibrosis. Dex may alleviate lung fibrosis and myofibroblast differentiation through the ADORA2B-mediated MAPK signaling pathway.
A multifunctional integrated biomimetic spore nanoplatform for successively overcoming oral biological barriers
Authors: Song Qingling , Yang Junfei , Wu Xiaocui , Li Yao , Zhao Hongjuan , Feng Qianhua , Zhang Zhenzhong , Zhang Yun , Wang Lei
Published: August 2023

The biological barriers have seriously restricted the efficacious responses of oral delivery system in diseases treatment. Utilizing a carrier based on the single construction means is hard to overcome these obstacles simultaneously because the complex gastrointestinal tract environment requires carrier to have different or even contradictory properties. Interestingly, spore capsid (SC) integrates many unique biological characteristics, such as high resistance, good stability etc. This fact offers a boundless source of inspiration for the construction of multi-functional oral nanoplatform based on SC without further modification. Herein, we develop a type of biomimetic spore nanoplatform (SC@DS NPs) to successively overcome oral biological barriers. Firstly, doxorubicin (DOX) and sorafenib (SOR) are self-assembled to form carrier-free nanoparticles (DS NPs). Subsequently, SC is effectively separated from probiotic spores and served as a functional vehicle for delivering DS NPs. As expect, SC@DS NPs can efficaciously pass through the rugged stomach environment after oral administration and further be transported to the intestine. Surprisingly, we find that SC@DS NPs exhibit a significant improvement in the aspects of mucus penetration and transepithelial transport, which is related to the protein species of SC. This study demonstrates that SC@DS NPs can efficiently overcome multiple biological barriers and improve the therapeutic effect.
“A peer support worker can really be there supporting the youth throughout the whole process”: a qualitative study exploring the role of peer support in providing substance use services to youth
Authors: Turuba Roxanne , Toddington Ciara , Tymoschuk Miranda , Amarasekera Anurada , Howard Amanda Madeleine , Brockmann Violet , Tallon Corinne , Irving Sarah , Mathias Steve , Henderson J. L. , Barbic Skye
Published: August 2023

Background

Youth (ages 12–24) rarely access services and supports to address substance use concerns. Peer support can facilitate service engagement and has been associated with positive substance use recovery outcomes in adults, yet few studies have examined this role among youth specifically. As such, this qualitative study explored the role of peer support in providing substance use services to youth in British Columbia and how best to support them in their role.

Methods

Participatory action research methods were used by partnering with youth who had lived/living experience of substance use, including peer support workers, to co-design the research protocol and materials. An initial focus group and subsequent interviews were held with 18 peer support workers who provide services to youth (ages 12–24) based on their own lived experience with mental health and/or substance use. The discussions were audio-recorded, transcribed verbatim, and analysed thematically using an inductive approach.

Results

Peer support workers' core experiences providing substance use services to youth centred around supporting youth throughout the whole process. This was accomplished by meeting youth where they are at, providing individualized care, and bridging the gap between other services and supports. However, participants experienced multiple organizational barriers hindering their ability to support youth and stressed the importance of having an employer who understands the work you are doing. This involved having someone advocating for the peer support role to promote collaboration, empowering peers to set boundaries and define their own role, and providing adequate training and mentorship. Finally, peer support workers described how their lived experience bridges connection and de-stigmatization at the individual, organizational, and community level, which was unique to their role.

Conclusions

Peer support plays a unique role in youths’ substance use journeys, given their own lived experience and flexibility within their role. However, their position is often misunderstood by employers and other service providers, leaving peers with inadequate support, training, and mentorship to do their job. The findings from this study call for improved integration of peer support into service environments, as well as standardized training that is in-depth and continuous.
Preliminary study on miRNA in prostate cancer
Authors: Abudoubari Saimaitikari , Bu Ke , Mei Yujie , Maimaitiyiming Abudukeyoumu , An Hengqing , Tao Ning
Published: August 2023

Objective

To screen for miRNAs differentially expressed in prostate cancer and prostate hyperplasia tissues and to validate their association with prostate cancer.

Methods

Patients diagnosed by pathology in the Department of Urology of the First Affiliated Hospital of Xinjiang Medical University from October 2021 to June 2022 were selected, and their general clinical information, blood samples, and prostate tissue samples were collected. miRNA microarray technology was performed to obtain differentially expressed miRNAs in prostate cancer and hyperplasia tissues, and miRNAs to be studied were screened by microarray results and review of relevant literature. The detection of miRNA expression in the patients’ blood and prostate tissue samples was measured. The miRNA-222-mimics were transfected into PC3 cells, and cell biology experiments such as CCK8, scratch, Transwell, and flow cytometry were performed to detect the effects of overexpressed miRNA-222 on the growth and proliferation, invasive ability, apoptotic ability, and metastatic ability of prostate cancer cells.

Results

The results of the miRNA microarray showed that there were many differentially expressed miRNAs in prostate cancer and hyperplasia tissues, and four miRNAs, miRNA-144, miRNA-222, miRNA-1248, and miRNA-3651 were finally selected as the subjects by reviewing relevant literature. The results showed that the expression of miRNA-222 in prostate cancer tissues was lower than that in prostate hyperplasia tissues (P < 0.05). The expression of miRNA-222, miRNA-1248, and miRNA-3651 in blood samples of prostate cancer patients was lower than that in prostate hyperplasia patients (P < 0.05). The analysis results indicated that the f/t ratio and the relative expression of miRNA-222 and miRNA-1248 were independent influences of prostate cancer (P < 0.05), in which overexpression of miRNA-222 decreased the proliferative, invasive, and metastatic abilities of PC3 cells and enhanced the level of apoptosis of cancer cells.

Conclusions

Although there was no significant change in the overall incidence of prostate cancer in this study, significant changes occurred in the incidence of prostate cancer with different characteristics. In addition, the nomogram prediction model of prostate cancer-specific survival rate constructed based on four factors has a high reference value, which helps physicians to correctly assess the patient-specific survival rate and provides a reference basis for patient diagnosis and prognosis evaluation.
Emerging SARS-CoV-2 variants of concern potentially expand host range to chickens: insights from AXL, NRP1 and ACE2 receptors
Authors: Lei Mengyue , Ma Ying , Chen Hongli , Huang Pu , Sun Jing , Wang Xu , Sun Qiangming , Hu Yunzhang , Shi Jiandong
Published: August 2023

Background

The possibilities of cross-species transmission of SARS-CoV-2 variants of concern (VOCs) between humans and poultry species are unknown. The analysis of the structure of receptor was used to investigate the potential of emerging SARS-CoV-2 VOCs to expand species tropism to chickens based on the interaction between Spike (S) protein and tyrosine kinase receptor UFO (AXL), angiotensin-converting enzyme 2 (ACE2), and neuropilin 1 (NRP1) with substantial public health importance.

Methods

The structural and genetic alignment and surface potential analysis of the amino acid (aa) in ACE2, AXL, and NRP1 in human, hamster, mouse, mink, ferret, rhesus monkey and chickens were performed by Swiss-Model and pymol software. The critical aa sites that determined the susceptibility of the SARS-CoV-2 to the host were screened by aligning the residues interfacing with the N-terminal domain (NTD) or receptor-binding domain (RBD) of Spike protein.

Results

The binding modes of chickens AXL and ACE2 to S protein are similar to that of the ferret. The spatial structure and electrostatic surface potential of NRP1 showed that SARS-CoV-2 VOCs could not invade chickens through NRP1 easily.

Conclusion

These results suggested that emerging SARS-CoV-2 VOCs potentially expand the host range to chickens mainly through ACE2 and AXL receptors, while NRP1 receptor may rarely participate in the future epidemic of coronavirus disease 2019 in chickens.
Isolation and pathogenicity of porcine circovirus type 2 in mice from Guangxi province, China
Authors: Jiao Qiulin , Yang Liuyue , Liu Xiangzu , Wen Yanwen , Tian Linxing , Qian Ping , Chen Huanchun , Li Xiangmin
Published: August 2023

Background

Porcine circovirus type 2 (PCV2), a member of the genus Circovirus and family Circoviridae, is a closed, small, circular, and single-stranded DNA virus, and it is a crucial swine pathogen of porcine circovirus-associated diseases (PCVADs). PCV2 was first detected in PK-15(ATCC-CCL) cells in 1974, which has caused significant economic loss to the swine industry throughout the world. And the first case of PCV2 was reported in China in 2000. At present, PCV2d is the main genotype circulating widely in China.

Methods

Lymph samples were obtained from piglets with emaciation and respiratory disease in Guangxi province, China. The main pathogens were detected via PCR from lymph samples, and then PCV2-single positive samples were used to inoculate with PK-15 cells. After successive generations, the isolate was subsequently identified by polymerase chain reaction (PCR), immunofluorescence assay (IFA), Western blot (WB), and transmission electron microscopic (TEM). The full-length genome and genetic characterization of isolates were analyzed by Sanger sequencing. The TCID50 of the PCV2-GX-6 was determined by IFA, and the pathogenicity of PCV2 in BALB/c mice was analyzed via the mouse model.

Results

The isolates were successfully isolated from clinical samples. The complete genome of PCV2-GX-4, PCV2-GX-6, PCV2-GX-7, PCV2-GX-11 and PCV2-GX-16 have been amplified, sequenced, and deposited in GenBank (accession no.: OR133747, OQ803314, OR133748, OR133749, OR133750). Homology and phylogenetic analysis with reference strains showed that the isolates belonged to the PCV2d genotype. The PCV2-GX-6 could be stably passaged more than 30 times in PK-15 cells. PCV2-GX-6 was identified by PCR, IFA, WB and TEM. The results of homology showed that PCV2-GX-6 was closely related to the reference strains PCV2-JS17-8 (GenBank accession no.: MH211363). Pathogenicity studies in mice have shown that PCV2-GX-6 can lead to growth inhibition of mice. Meanwhile PCV2-GX-6 caused the typical lesions of spleen, lung and kidney. The results of qPCR showed that PCV2 can effectively proliferate in the liver, spleen, lung, and kidney.

Conclusion

PCV2-GX-6 can successfully infect BLAB/c mice, effectively proliferate in major organs, and possessed high pathogenicity. In conclusion, combined with the genotype and pathogenicity of PCV2d currently prevalent, PCV2-GX-6 can be used as a candidate vaccine strain.
Exploring electronic cigarette portrayals: a content and thematic analysis of African online news coverage
Authors: Ngoma Chimwemwe , Adebisi Yusuff Adebayo
Published: August 2023

Background

Electronic cigarette use has surged internationally in recent years, with numerous countries noting an uptick in users. Despite this, the portrayal of e-cigarette usage in African news remains unclear.

Methods

This research investigates the subject, employing a mixed-methodology approach. The study units were news articles on electronic cigarette use retrieved from AllAfrica, an online African news archive. A total of 38 online news and opinion articles published between June 2017 and June 2022 qualified the exclusion and inclusion criteria. A content analysis revealed prevalent codes and themes, while a thematic analysis explored the association between news sources and framing.

Results

The results indicate that articles and arguments presenting e-cigarettes positively outnumber those with a negative slant. The health impacts of electronic cigarettes emerged as the most discussed topic, with health authorities frequently cited as news sources. However, these health authorities often lacked a unified stance on e-cigarette safety.

Conclusion

The lack of consensus among health officials could have public health consequences, possibly resulting in the formulation of uninformed policies.
Effect of diabetes mellitus on the outcomes of total ankle arthroplasty: is controlled diabetes mellitus a risk factor?
Authors: Lee Gun-Woo , Jung Dong-Min , Jung Woo-Chul , Lee Keun-Bae
Published: August 2023

Background

It is still uncertain whether diabetes mellitus (DM) is a risk factor for poor outcomes and increased complications after total ankle arthroplasty (TAA). The objective of this study was to compare clinical outcomes and complication rates of TAA in patients with and without DM.

Methods

This study enrolled patients with symptomatic end-stage ankle osteoarthritis with a minimum follow-up period of 24 months after TAA. A total of 252 patients (266 ankles) were classified into two groups according to the presence of DM: (1) DM group (59 patients, 67 ankles) and (2) non-DM group (193 patients, 199 ankles). We defined controlled diabetes as (1) HbA1c level < 7.0%, or (2) fasting glucose level < 130 mg/dL with HbA1c level ≥ 7.0% for hospitalization period. Clinical outcomes data (Ankle Osteoarthritis Scale, American Orthopedic Foot and Ankle Society ankle-hindfoot score, Short Form-36 Physical Component Summary score, and visual analog scale for pain) were compared preoperatively and at the final follow-up between the two groups. Complications following TAA were also compared between the two groups.

Results

All clinical variables had improved in both groups by the final follow-up (mean follow-up = 77.8 months). There was no significant difference in any clinical variable between the two groups at the final follow-up (P > 0.05). Of the 266 ankles, 73 ankles (19 in the DM group, 54 in the non-DM group) developed periprosthetic osteolysis. Although the DM group showed a higher prevalence of aseptic loosening or subsidence, the difference between the two groups was not statistically significant (P = 0.236).

Conclusions

In the intermediate-term follow-up, TAA in patients with controlled DM showed clinical outcomes and complication rates comparable to patients without DM. Our results suggest that TAA can be done safely in diabetic patients if the DM is controlled in the perioperative period.

Level of evidence: Therapeutic Level III.
Pure uniportal video-assisted thoracic surgery for treating thoracic tuberculous spondylitis: an initial case series of seven patients
Authors: Xiu Xin , Chen Yungang , Ding Yonghua , Zhang Qiang , Chen Deqiang
Published: August 2023

Background

The development of thoracic surgical techniques has provided a new avenue for treating thoracic tuberculosis. Moreover, microscopic treatment of spinal tuberculosis has attracted increasing attention, as it affords good visual access and reduces trauma. Traditional thoracoscopic treatment of spinal tuberculosis usually requires 2–3 passages, accompanied by a corresponding number of incisions. With a large number of conventional thoracoscopic surgeries performed, improved resolution of the microscopic field of view, effective hemostasis of the peripheral vessels using the ultrasonic knife, and many reports in the literature, thoracic tuberculosis can now be treated microscopically by creating a single channel. The aim of this study was to explore the feasibility and surgical technique for thoracic tuberculous spondylitis treatment via debridement and bone graft fusion surgery employing pure uniportal video-assisted thoracic surgery (VATS), combined with posterior internal fixation.

Methods

Seven patients with relatively complete documentation were included in this study. All patients underwent lesion removal and bone graft reconstruction via uniportal VATS with posterior internal fixation. The mean patient age was 39.6 years. Surgical duration, blood loss volume, postoperative recovery time, and thoracic kyphosis angle were recorded.

Results

The surgeries were successful with no severe postoperative complications. All patients were followed-up, and no recurrence of tuberculosis was observed. Imaging data, including computed tomography scans, confirmed the complete removal of the lesions. Additionally, bone fusion at the graft site was successful, no loss of the thoracic kyphosis angle was noted postoperatively, and the thoracic kyphosis angle improved.

Conclusions

Pure uniportal VATS yields satisfactory results and inflicts less trauma than previous surgical techniques. This technique also offers a reference value for treating thoracic tuberculous spondylitis.
Overcoming challenges in rare disease registry integration using the semantic web - a clinical research perspective
Authors: Gisslander Karl , Mohammad Aladdin J , Vaglio Augusto , Little Mark A
Published: August 2023

The growing number of disease-specific patient registries for rare diseases has highlighted the need for registry interoperability and data linkage, leading to large-scale rare disease data integration projects using Semantic Web based solutions. These technologies may be difficult to grasp for rare disease experts, leading to limited involvement by domain expertise in the data integration process. Here, we propose a data integration framework starting from the perspective of the clinical researcher, allowing for purposeful rare disease registry integration driven by clinical research questions.
Congenital disorders of glycosylation: narration of a story through its patents
Authors: Monticelli Maria , D’Onofrio Tania , Jaeken Jaak , Morava Eva , Andreotti Giuseppina , Cubellis Maria Vittoria
Published: August 2023

Congenital disorders of glycosylation are a group of more than 160 rare genetic defects in protein and lipid glycosylation. Since the first clinical report in 1980 of PMM2-CDG, the most common CDG worldwide, research made great strides, but nearly all of them are still missing a cure. CDG diagnosis has been at a rapid pace since the introduction of whole-exome/whole-genome sequencing as a diagnostic tool. Here, we retrace the history of CDG by analyzing all the patents associated with the topic. To this end, we explored the Espacenet database, extracted a list of patents, and then divided them into three major groups: (1) Drugs/therapeutic approaches for CDG, (2) Drug delivery tools for CDG, (3) Diagnostic tools for CDG. Despite the enormous scientific progress experienced in the last 30 years, diagnostic tools, drugs, and biomarkers are still urgently needed.
Automated assessment of foot elevation in adults with hereditary spastic paraplegia using inertial measurements and machine learning
Authors: Ollenschläger Malte , Höfner Patrick , Ullrich Martin , Kluge Felix , Greinwalder Teresa , Loris Evelyn , Regensburger Martin , Eskofier Bjoern M. , Winkler Jürgen , Gaßner Heiko
Published: August 2023

Background

Hereditary spastic paraplegias (HSPs) cause characteristic gait impairment leading to an increased risk of stumbling or even falling. Biomechanically, gait deficits are characterized by reduced ranges of motion in lower body joints, limiting foot clearance and ankle range of motion. To date, there is no standardized approach to continuously and objectively track the degree of dysfunction in foot elevation since established clinical rating scales require an experienced investigator and are considered to be rather subjective. Therefore, digital disease-specific biomarkers for foot elevation are needed.

Methods

This study investigated the performance of machine learning classifiers for the automated detection and classification of reduced foot dorsiflexion and clearance using wearable sensors. Wearable inertial sensors were used to record gait patterns of 50 patients during standardized 4 $$\times$$
×
 10 m walking tests at the hospital. Three movement disorder specialists independently annotated symptom severity. The majority vote of these annotations and the wearable sensor data were used to train and evaluate machine learning classifiers in a nested cross-validation scheme.

Results

The results showed that automated detection of reduced range of motion and foot clearance was possible with an accuracy of 87%. This accuracy is in the range of individual annotators, reaching an average accuracy of 88% compared to the ground truth majority vote. For classifying symptom severity, the algorithm reached an accuracy of 74%.

Conclusion

Here, we show that the present wearable gait analysis system is able to objectively assess foot elevation patterns in HSP. Future studies will aim to improve the granularity for continuous tracking of disease severity and monitoring therapy response of HSP patients in a real-world environment.
Analysis of the genetic contribution to thoracic aortic aneurysm or dissection in a prospective cohort of patients with familial and sporadic cases in East China
Authors: Duan Yanyu , Xiong Jianxian , Lai Zhenghong , Zhong Yiming , Tian Chengnan , Du Zhiming , Luo Zhifang , Yu Junjian , Li Wentong , Xu Weichang , Wang Yabing , Ding Ting , Zhong Xuehong , Pan Mengmeng , Qiu Yu , Lan Xuemei , Chen Taihua , Li Peijun , Liu Kang , Gao Meng , Hu Yanqiu , Liu Ziyou
Published: August 2023

Background

Thoracic aortic aneurysm or dissections (TAADs) represent a group of life-threatening diseases. Genetic aetiology can affect the age of onset, clinical phenotype, and timing of intervention. We conducted a prospective trial to determine the prevalence of pathogenic variants in TAAD patients and to elucidate the traits related to harbouring the pathogenic variants. One hundred and one unrelated TAAD patients underwent genetic sequencing and analysis for 23 TAAD-associated genes using a targeted PCR and next-generation sequencing-based panel.

Results

A total of 47 variants were identified in 52 TAAD patients (51.5%), including 5 pathogenic, 1 likely pathogenic and 41 variants of uncertain significance. The pathogenic or likely pathogenic (P/LP) variants in 4 disease-causing genes were carried by 1 patient with familial and 5 patients with sporadic TAAD (5.9%). In addition to harbouring one variant causing familial TAAD, the FBN1 gene harboured half of the P/LP variants causing sporadic TAAD. Individuals with an age of onset less than 50 years or normotension had a significantly increased genetic risk.

Conclusions

TAAD patients with a younger age at diagnosis or normotension were more likely to carry a P/LP variant; thus, routine genetic testing will be beneficial to a better prognosis through genetically personalized care prior to acute rupture or dissection.
Economic burden of adult patients with β-thalassaemia major in mainland China
Authors: Zhen Xuemei , Ming Jing , Zhang Runqi , Zhang Shuo , Xie Jing , Liu Baoguo , Wang Zijing , Sun Xiaojie , Shi Lizheng
Published: August 2023

Background

β-thalassaemia major poses a substantial economic burden, especially in adults. We aimed to estimate the economic burden of adult patients with β-thalassaemia major from a societal perspective using the real-world data. According to the clinical guideline, we also estimated the annual medical costs for patients with the same body weight and calculated the lifetime medical costs over 50 years in mainland China.

Methods

This was a retrospective cross-sectional study. An online survey with snowball sampling covering seven provinces was conducted. We extracted patient demographics, caregiver demographics, disease and therapy information, caring burden, and costs for adult patients diagnosed with β-thalassaemia major and their primary caregivers. In the real world, we estimated the annual direct medical cost, direct nonmedical cost, and indirect cost. In addition, we calculated the annual direct medical cost and lifetime direct medical cost by weight with discounted and undiscounted rates according to the clinical guideline.

Results

Direct medical costs was the main driver of total cost, with blood transfusion and iron chelation therapy as the most expensive components of direct medical cost. In addition, adult patients with β-thalassaemia major weighing 56 kg were associated with an increase of $2,764 in the annual direct medical cost using the real-world data. The undiscounted and discounted (5% discount rate) total lifetime treatment costs were $518,871 and $163,441, respectively.

Conclusions

Patients with β-thalassaemia major often encounter a substantial economic burden in mainland China. Efforts must be made to help policymakers develop effective strategies to reduce the burden and pevalence of thalassaemia.
Identification of two novel SALL1 mutations in chinese families with townes-brocks syndrome and literature review
Authors: Wang Zhendong , Sun Zhenfu , Diao Yujie , Wang Zhouyang , Yang Xiangdong , Jiang Bei , Wu Yumei , Liu Guangyi
Published: August 2023

Background

Townes-Brocks syndrome is a rare autosomal dominant genetic syndrome caused by mutations in SALL1. The clinical features of Townes-Brocks syndrome are highly heterogonous. Identification of new SALL1 mutations and study of the relation between SALL1 mutations and clinical features can facilitate diagnosis of Townes-Brocks syndrome.

Methods

We collected clinical data and blood samples of the two patients and their family members for whole-exome sequencing and Sanger sequencing. Prediction analysis of the SALL1variation protein structure was achieved using Alphafold. The clinical materials and gene sequencing results were analyzed. The clinical materials and gene sequencing results were analyzed. The related literature of Townes-Brocks syndrome were searched and the genotype-renal phenotype analysis was performed combined with this two cases.

Results

Based on the clinical features and gene sequencing results, the two patients were diagnosed as Townes-Brocks syndrome. Two novel SALL1 mutations (c.878-887del and c.1240G > T) were identified, both of which were pathogenic mutations. The correlation between genotypes and renal phenotypes in Townes-Brocks syndrome patients caused by SALL1 mutation were summarized.

Conclusion

This study identified two novel mutations and provided new insights into the correlation of genotypes and renal phenotypes of Townes-Brocks syndrome.
Lumbar vertebral canal stenosis due to marked bone overgrowth after routine hemilaminectomy in a dog
Authors: Tavola Francesca , Ruggeri Marco , Carrera Ines , Pumarola Martí , Alegria Pablo Menendez , Tauro Anna
Published: August 2023

Background

Bone overgrowth after decompressive surgery for lumbar stenosis resulting in recurrence of neurological signs has not been reported in veterinary literature. However, there are few cases described in human medicine.

Case presentation

A 13-month-old entire female dog, a crossbreed between a Springer Spaniel and a Border Collie, weighing 24 kg, was referred with a 5-day history of progressive spastic paraplegia, indicative of a T3-L3 myelopathy. Magnetic resonance (MR) imaging revealed a right-sided L2-L3 compressive extradural lesion, compatible with epidural haemorrhage, which was confirmed by histopathology. The lesion was approached via right-sided L2-L3 hemilaminectomy and was successfully removed. One-year postoperatively the dog re-presented with pelvic limb ataxia. MR and computed tomography (CT) images demonstrated excessive vertebral bone formation affecting the right articular processes, ventral aspect of the spinous process of L2-L3, and contiguous vertebral laminae, causing spinal cord compression. Revision surgery was performed, and histopathology revealed normal or reactive osseous tissue with a possible chondroid metaplasia and endochondral ossification, failing to identify a definitive reason for the bone overgrowth. Nine-month postoperatively, imaging studies showed a similar vertebral overgrowth, resulting in minimal spinal cord compression. The patient remained stable with mild proprioceptive ataxia up until the last follow-up 18 months post-revision surgery.

Conclusion

This is the first report in the veterinary literature of bone overgrowth after lumbar hemilaminectomy which resulted in neurological deficits and required a revision decompressive surgery.
Physicians in police tactical teams – ethical considerations
Authors: de Valence Timothee , Suppan Laurent
Published: August 2023

High-profile mass shootings, terrorist attacks, and experience acquired during recent conflicts have led to a shift in police tactics, who now follow an aggressive approach to immediately neutralize the threat in addition to providing early tactical medical care. A growing number of police tactical teams now include physicians in their ranks to increase the level of forward care. Many ethical questions arise from having physicians on police tactical teams, such as the notion of risk, the use of force, and the ultimate role the physician is expected to play. Having a physician in such a team may be an invaluable asset to increase the team’s safety and allow for advanced forward care, however, this requires two important conditions. The first is that the role of the physician is clearly defined and that what is expected of him is in line with medical ethics, while the second is extensive tactical training with the team to collaborate flawlessly in this complex, high-stress environment.
Determinants of incident atherosclerotic cardiovascular disease events among individuals with type 2 diabetic microvascular complications in the UK: a prospective cohort study
Authors: Wang Yaxin , Bulloch Gabriella , Huang Yu , Liang Yingying , Du Zijing , Wu Guanrong , Fang Ying , Hu Yijun , Shang Xianwen , Zhu Zhuoting , Zhang Xiayin , Yang Xiaohong , Yu Honghua
Published: August 2023

Objective

To evaluate the association of atherosclerotic cardiovascular disease (ASCVD) risk factors with incident ASCVD events among type 2 diabetes (T2D) individuals with microvascular complications.

Methods

We included T2D participants with only microvascular complications from the UK Biobank cohort at baseline (2006–2010). Multivariable-adjusted Cox proportional hazards models were used to study the association between ASCVD risk factors with adjudicated incident ASCVD in T2D participants with only microvascular complications. A restricted cubic spline approach was employed to evaluate potential nonlinear associations between ASCVD risk factors and ASCVD.

Results

We studied 4,129 T2D individuals with microvascular complications at baseline. Over a median follow-up of 11.7 years, a total of 1,180 cases of incident ASCVD were documented, of which 1,040 were CHD, 100 were stroke, and 40 were both CHD and stroke events. After multivariable-adjustment, high-density lipoprotein cholesterol (HDL-C) level was linearly associated with a decreased risk of incident ASCVD [hazard ratio (HR): 0.49, 95% Confidence interval (CI): 0.32–0.75, Plinear = 0.011] and each 10 nmol/L increase of lipoprotein(a) [Lp(a)] level (HR: 1.02, 95% CI: 1.00-1.04, Plinear = 0.012) was linearly associated with an increased risk of incident ASCVD in T2D participants with only microvascular complications.

Conclusion

HDL-C levels and Lp(a) levels (per 10 nmol/L) showed an independent linear relation with ASCVD risk among T2D individuals with only microvascular complications at long-term follow-up.
Association of DNA methylation of vitamin D metabolic pathway related genes with colorectal cancer risk
Authors: Wang Yi-Fan , Li Lei , Deng Xue-Qing , Fang Yu-Jing , Zhang Cai-Xia
Published: August 2023

Background

Vitamin D might have anti-tumor effect, which is affected by the genes related to vitamin D metabolic pathway. Epigenetic mechanism may affect the expression level of vitamin D metabolic pathway related genes, then plays an important role in the occurrence and development of colorectal cancer. To date, no study has reported on the association between blood-based DNA methylation level of vitamin D metabolic pathway related genes and colorectal cancer risk.

Methods

A case–control study was conducted including 102 colorectal cancer cases and 102 sex- and age-frequency-matched controls in Guangzhou, China. CpG islands in the VDR, CYP24A1, CYP27B1 and CYP2R1 genes were chosen for DNA methylation analysis by MethylTarget sequencing. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of DNA methylation levels for colorectal cancer. Taking the point with the largest Youden index as the boundary value, the cumulative methylation levels of vitamin D metabolic pathway related genes were divided into hypomethylation and hypermethylation. Unconditional multivariable logistical regression model was used to calculate the adjusted odds ratio (aOR) and 95% confidence intervals (95% CIs) after adjusting for potential confounders.

Results

Among 153 CpG sites, 8 CpG sites were significantly different between the cases and the controls. The cumulative methylation level of all CpG sites in CYP2R1 was inversely associated with the risk of colorectal cancer (aOR, 0.49; 95% CI, 0.26–0.91). However, no significant association was found between cumulative methylation levels of all CpG sites in VDR, CYP24A1 and CYP27B1 and colorectal cancer risk. Significant inverse association was observed between cumulative methylation level of significant CpG sites in VDR (aOR, 0.28; 95% CI, 0.16–0.51) and CYP24A1 (aOR, 0.19; 95% CI, 0.09–0.40) and colorectal cancer risk. There were no significant associations between cumulative methylation levels of significant CpG sites in CYP2R1 and CYP27B1 and colorectal cancer risk.

Conclusions

This study indicated that the cumulative methylation levels of significant CpG sites in VDR and CYP24A1 and all CpG sites in CYP2R1 were inversely associated with colorectal cancer risk.
Cyclosporine for omalizumab-refractory chronic urticaria: a report of five cases
Authors: LaCava Anthony F. , Fadugba Olajumoke O.
Published: August 2023

Background

While both the AAAAI/ACAAI and the EAACI/GA2LEN/EuroGuiDerm/APAAACI guidelines recommend starting cyclosporine for patients with chronic urticaria who have had an inadequate response to omalizumab, many clinicians are hesitant to initiate cyclosporine due to paucity of clinical data. The objective of this study was to report real-life clinical outcomes in adult patients with chronic urticaria who had an inadequate response to omalizumab and were switched from omalizumab to cyclosporine. Medical records of adult patients with chronic urticaria who had an inadequate response with omalizumab and were later treated with cyclosporine were reviewed retrospectively. Data pertaining to treatment method, clinical response, and adverse effects were recorded.

Results/presentation of cases

Five patients with omalizumab-refractory chronic urticaria, three of whom also had angioedema and one with an inducible urticaria, were treated with low doses of oral cyclosporine (1–3 mg/kg/d). Four of five patients in this case series had complete resolution of symptoms with oral cyclosporine, while continuing other standard therapies. Systemic side effects occurred in three patients which prompted drug discontinuation in two patients.

Discussion

Cyclosporine alone was effective in inducing urticaria control in adult patients with chronic urticaria who had an inadequate response to omalizumab, though the impact of cyclosporine was limited by reversible adverse effects. Adverse effects were associated with pre-existing medical conditions. As novel chronic urticaria therapies are being investigated, this experience highlights the importance of uncovering chronic urticaria subtypes which tend to respond to cyclosporine, while providing alternative treatments with better tolerability.
Long-term persistence of piscine orthoreovirus-1 (PRV-1) infection during the pre-smolt stages of Atlantic salmon in freshwater
Authors: Kannimuthu Dhamotharan , Roh HyeongJin , Peñaranda Ma. Michelle D. , Wessel Øystein , Mæhle Stig , Berhe Ghebretnsae Dawit , Nordbø Joachim , Kvamme Bjørn Olav , Morton H. Craig , Grove Søren
Published: August 2023

Piscine orthoreovirus (PRV) causes heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon. During salmon production cycles, HSMI has predominantly been observed after seawater transfer. More recently, better surveillance and longitudinal studies have detected occurrences of PRV-1 in freshwater broodstock farms and hatcheries. However, very little is known about the viral kinetics of PRV-1 or disease development of HSMI during these pre-smolt stages. In this study, we conducted a long-term PRV-1 challenge experiment to examine the profile of viral load, infectiousness and/or clearance in Atlantic salmon during their development from fry to parr stage. Atlantic salmon fry (mean weight: 1.1 ± 0.19 g) were infected with PRV-1 (high virulent variant) via intraperitoneal (IP) injection. The viral load reached a peak at 2–4 weeks post-challenge (wpc) in heart and muscle tissues. The virus was detected at relatively high levels in whole blood, spleen, and head kidney tissues until 65 wpc. Heart and muscle lesions typical of HSMI were clearly observed at 6 and 8 wpc but then subsided afterwards resolving inflammation. Innate and adaptive immune responses were elicited during the early/acute phase but returned to basal levels during the persistent phase of infection. Despite achieving high viremia, PRV-1 infection failed to cause any mortality during the 65-week virus challenge period. Cohabitation of PRV-1 infected fish (10 and 31 wpc) with naïve Atlantic salmon fry resulted in very low or no infection. Moreover, repeated chasing stress exposures did not affect the viral load or shedding of PRV-1 at 26 and 44 wpc. The present findings provide knowledge about PRV-1 infection in juvenile salmon and highlight the importance of continued monitoring and management to prevent and mitigate the PRV-1 infection in freshwater facilities.
The therapeutic potential for targeting CSE/H2S signaling in macrophages against Escherichia coli infection
Authors: Fu Shaodong , Wang Zhenglei , Han Xiangan , Xu Yuanyuan , Miao Jinfeng
Published: August 2023

Macrophages play a pivotal role in the inflammatory response to the zoonotic pathogen E. coli, responsible for causing enteric infections. While considerable research has been conducted to comprehend the pathogenesis of this disease, scant attention devoted to host-derived H2S. Herein, we reported that E. coli infection enhanced the expression of CSE in macrophages, accompanied by a significantly increased inflammatory response. This process may be mediated by the involvement of excessive autophagy. Inhibition of AMPK or autophagy with pharmacological inhibitors could alleviate the inflammation. Additionally, cell model showed that the mRNA expression of classic inflammatory factors (Il-1β, Il-6), macrophage polarization markers (iNOS, Arg1) and ROS production was significantly down-regulated after employing CSE specific inhibitor PAG. And PAG is capable of inhibiting excessive autophagy through the LKB1-AMPK-ULK1 axis. Interestingly, exogenous H2S could suppress inflammation response. Our study emphasizes the importance of CSE in regulating the macrophage-mediated response to E. coli. Increased CSE in macrophages leads to excessive inflammation, which should be considered a new target for drug development to treat intestinal infection.
Performance of RIS-aided near-field localization under beams approximation from real hardware characterization
Authors: Rahal Moustafa , Denis Benoît , Keykhosravi Kamran , Keskin Musa Furkan , Uguen Bernard , Alexandropoulos George C. , Wymeersch Henk
Published: August 2023

The technology of reconfigurable intelligent surfaces (RISs) has been showing promising potential in a variety of applications relying on Beyond-5G networks. RIS can indeed provide fine channel flexibility to improve communication quality of service (QoS) or restore localization capabilities in challenging operating conditions, while conventional approaches fail (e.g., due to insufficient infrastructure, severe radio obstructions). In this paper, we tackle a general low-complexity approach for optimizing the precoders that control such reflective surfaces under hardware constraints. More specifically, it allows the approximation of any desired beam pattern using a pre-characterized lookup table of feasible complex reflection coefficients for each RIS element. The proposed method is first evaluated in terms of beam fidelity for several examples of RIS hardware prototypes. Then, by means of a theoretical bounds analysis, we examine the impact of RIS beams approximation on the performance of near-field downlink positioning in non-line-of-sight conditions, while considering several RIS phase profiles (including directional, random and localization-optimal designs). Simulation results in a canonical scenario illustrate how the introduced RIS profile optimization scheme can reliably produce the desired RIS beams under realistic hardware limitations. They also highlight its sensitivity to both the underlying hardware characteristics and the required beam kinds in relation to the specificity of RIS-aided localization applications.
“I think it is woven through me, and sadly that means it is woven through our family life”: the experiences and support needs of mothers with eating disorders
Authors: Chapman Laura , Cartwright-Hatton Sam , Lester Kathryn J.
Published: August 2023

Background

Eating disorders may disrupt parenting, and there is evidence to suggest that the children of parents with eating disorders are at greater risk for the development of eating disorders themselves. This study sought to broaden and extend current understandings of the lived experiences of mothers who have eating disorders.

Method

A qualitative study using thematic analysis was conducted. Eighteen mothers living in the UK, USA, and Australia took part in semi-structured online interviews. Participants were mothers to at least one child aged two years or older, had received a lifetime diagnosis of one or more eating disorders, and reported experiencing symptoms since becoming a parent.

Results

Data were analysed using an inductive approach to reflexive thematic analysis. Four major themes, each with subthemes, were identified. These were: parenthood as a double-edged sword; the eating disorder impacts on parenting; blame and burden; and seeking support.

Conclusions

The lived experiences of mothers indicate a complex relationship between eating disorders and parenthood. While parenting can impact eating disorders, eating disorders can also impact parenting, in a range of ways that extend beyond the domains of food, eating and the body. There is a pressing need for the development of specialised, non-judgemental support options for parents with eating disorders and their families.
Intraperitoneal ropivacaine with dexamethasone versus ropivacaine alone for pain relief after laparoscopic cholecystectomy: a randomized prospective trial
Authors: Jadav Deepa , Wadhawa Reema , Vaishnav Barkha
Published: August 2023

Background

Intraperitoneal instillation of local anesthetics provides effective postoperative pain control after laparoscopic cholecystectomy (LC). This study was aimed to evaluate the analgesic effect and effects on postoperative nausea and vomiting (PONV) of intraperitoneal ropivacaine alone and with dexamethasone in patients undergoing LC. In this randomized, prospective, double-blinded, observational clinical study, a total of 100 patients scheduled for LC were randomized into two equal groups. Group RD (n = 50) received 0.2% ropivacaine 30 ml plus 8 mg dexamethasone, and group RS (n = 50) received 0.2% ropivacaine 30 ml plus 2 ml normal saline intraperitoneally at the end of surgery through the trocar. Pain score was monitored using a numeric rating scale (NRS) at 0, 1, 2, 4, 6, 12, and 24 h postoperatively. The primary objective of the study was to compare the pain intensity between the groups. The secondary objectives were to compare the time to first rescue analgesia, total dose of rescue analgesic in 24 h, incidence of PONV, and side effects if any between the groups.

Results

A significant difference in mean NRS score was observed among two groups at 6, 12, and 24 h. Only 52% in group RD demanded rescue analgesia as compared to 76% in group RS (P = 0.0004). Incidence of PONV was significantly lower in the RD group than in the RS group. No significant adverse effects were found.

Conclusions

The addition of 8 mg dexamethasone to intraperitoneal ropivacaine (0.2%) significantly prolongs the time of first rescue analgesic requirement and reduces the total consumption of rescue analgesic in 24 h. It significantly reduces the incidence of PONV in LC as compared to ropivacaine use alone.

Trial registration

The clinical trial is registered under Clinical Trials Registry—India

Registration no.: CTRI/2021/10/037206