bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellulitis caused by Roseomonas mucosa in a child: a case report
Authors: Matsuhisa Yuki , Kenzaka Tsuneaki , Hirose Hideo , Gotoh Tadao
Published: December 2023

Background

Roseomonas mucosa (R. mucosa) is a pink-pigmented, Gram-negative short rod bacterium. It is isolated from moist environments and skin, resistant to multiple drugs, including broad-spectrum cephalosporins, and a rare cause of infection with limited reports. R. mucosa mostly causes catheter-related bloodstream infections, with even fewer reports of skin and soft tissue infections.

Case presentation

A 10-year-old boy received topical steroid treatment for sebum-deficient eczema. A few days before the visit, he was bitten by an insect on the front of his right lower leg and scratched it due to itching. The day before the visit, redness, swelling, and mild pain in the same area were observed. Based on his symptoms, he was diagnosed with cellulitis. He was treated with sulfamethoxazole/trimethoprim, and his symptoms improved. Pus culture revealed R. mucosa.

Conclusions

We report a rare case of cellulitis caused by R. mucosa. Infections caused by rare organisms that cause opportunistic infections, such as R. mucosa, should be considered in patients with compromised skin barrier function and regular topical steroid use. Gram stain detection of organisms other than Gram-positive cocci should be considered.
Non-pharmacological therapy for chemotherapy-induced peripheral neurotoxicity: a network meta-analysis of randomized controlled trials
Authors: Zhang Xia , Wang Ao , Wang Miaowei , Li Guo , Wei Quan
Published: December 2023

Background

Chemotherapy-induced peripheral neurotoxicity (CIPN) is the most common adverse effect in patients undergoing chemotherapy, and no effective interventions are currently available for its prevention and treatment. Non-pharmacological therapies appear to be beneficial for the prevention and treatment of CIPN, but it remains unclear which therapy is most effective. The aim of this study was to identify the most effective non-pharmacological therapy for CIPN patients.

Methods

PubMed, Web of Science, Embase, and Cochrane Library were searched for randomized controlled trials on non-pharmacological therapies for CIPN. The primary outcomes included pain and peripheral neuropathological symptoms, and the secondary outcomes included quality of life, sensory and motor symptoms. The pairwise analysis and a network meta-analysis were performed using a random effects model.

Results

A total of 46 articles were included in this study, involving 2,878 participants. Our study showed that massage was more effective in pain-alleviating compared with acupuncture [SMD = 0.81, 95%CI (0.04, 1.57)], vitamin and gabapentin [SMD = 2.56, 95%CI (1.39, 3.74)], and usual care and placebo [SMD = 0.9, 95%CI (0.31, 1.49)]. As for attenuating peripheral neuropathological symptoms, massage was more effective than usual care and placebo [SMD = 0.75, 95%CI (0.33, 1.17)], sensorimotor training [SMD = 1.17, 95%CI (0.24, 2.10)], electrostimulation [SMD=-1.18, 95%CI (-2.14, -0.21)], multimodal exercise [SMD=-0.82, 95%CI (-1.57, -0.08)], and resistance training [SMD = 1.03, 95%CI (0.11, 1.95)]. Massage was also more effective than other non-pharmacological therapies in improving quality of life, sensory and motor symptoms.

Conclusions

According to our study, massage has advantages in alleviating pain, improving quality of life, and improving peripheral neuropathological symptoms and has better effect than other non-pharmacological interventions, representing certain clinical significance. However, the results of this study should be interpreted with caution due to the limitations of the included studies. In the future, more high-quality multi arm randomized controlled trials can be attempted to provide direct comparisons of the relative effects of non-pharmacological interventions.
Adjunct prednisone in community-acquired pneumonia: 180-day outcome of a multicentre, double-blind, randomized, placebo-controlled trial
Authors: Blum Claudine A. , Roethlisberger Eva A. , Cesana-Nigro Nicole , Winzeler Bettina , Rodondi Nicolas , Blum Manuel R. , Briel Matthias , Mueller Beat , Christ-Crain Mirjam , Schuetz Philipp
Published: December 2023

Background

Several trials and meta-analyses found a benefit of adjunct corticosteroids for community-acquired pneumonia with respect to short-term outcome, but there is uncertainty about longer-term health effects. Herein, we evaluated clinical outcomes at long term in patients participating in the STEP trial (Corticosteroid Treatment for Community-Acquired Pneumonia).

Methods

This predefined secondary analysis investigated 180-day outcomes in 785 adult patients hospitalized with community-acquired pneumonia included in STEP, a randomised, placebo-controlled, double-blind trial. The primary endpoint was time to death from any cause at 180 days verified by telephone interview. Additional secondary endpoints included pneumonia-related death, readmission, recurrent pneumonia, secondary infections, new hypertension, and new insulin dependence.

Results

From the originally included 785 patients, 727 were available for intention-to-treat analysis at day 180. There was no difference between groups with respect to time to death from any cause (HR for corticosteroid use 1.15, 95% CI 0.68 to 1.95, p = 0.601). Compared to placebo, corticosteroid-treated patients had significantly higher risks for recurrent pneumonia (OR 2.57, 95% CI 1.29 to 5.12, p = 0.007), secondary infections (OR 1.94, 95% CI 1.25 to 3.03, p = 0.003) and new insulin dependence (OR 8.73, 95% CI 1.10 to 69.62, p = 0.041). There was no difference regarding pneumonia-related death, readmission and new hypertension.

Conclusions

In patients with community-acquired pneumonia, corticosteroid use was associated with an increased risk for recurrent pneumonia, secondary infections and new insulin dependence at 180 days. Currently, it is uncertain whether these long-term adverse effects outweigh the short-term effects of corticosteroids in moderate CAP.

Trial registration

This trial was registered with ClinicalTrials. gov, number NCT00973154 before the recruitment of the first patient. First posted: September 9, 2009. Last update posted: April 21, 2015.
Common salt aggravated pathology of testosterone-induced benign prostatic hyperplasia in adult male Wistar rat
Authors: Bello Idris Idowu , Omigbodun Akinyinka , Morhason-Bello Imran
Published: December 2023

Background

Benign prostatic hyperplasia (BPH) is a major health concern associated with lower urinary tract symptoms and sexual dysfunction in men. Recurrent inflammation, decreased apoptotic rate and oxidative stress are some of the theories that explain the pathophysiology of BPH. Common salt, a food additive, is known to cause systemic inflammation and redox imbalance, and may serve as a potential risk factor for BPH development or progression. This study examined the effect of common salt intake on the pathology of testosterone-induced BPH.

Methods

Forty male Wistar rats were randomly divided into four equal groups of 10: a control and three salt diet groups-low-salt diet (LSD), standard-salt diet (SSD) and high-salt diet (HSD). The rats were castrated, allowed to recuperate and placed on salt-free diet (control), 0.25% salt diet (LSD), 0.5% salt diet (SSD) and 1.25% salt diet (HSD) for 60 days ad libitum. On day 33, BPH was induced in all the rats with daily injections of testosterone propionate-Testost® (3 mg/kg body weight) for 28 days. The rats had overnight fast (12 h) on day 60 and were euthanized the following day in order to collect blood and prostate samples for biochemical, molecular and immunohistochemistry (IHC) analyses. Mean ± SD values were calculated for each group and compared for significant difference with ANOVA followed by post hoc test (Tukey HSD) at p < 0.05.

Results

This study recorded a substantially higher level of IL-6, IL-8 and COX-2 in salt diet groups and moderate IHC staining of COX-2 in HSD group. The prostatic level of IL-17, IL-1β, PGE2, relative prostate weight and serum PSA levels were not statistically different. The concentrations of IGF-1, TGF-β were similar in all the groups but there were multiple fold increase in Bcl-2 expression in salt diet groups-LSD (13.2), SSD (9.5) and HSD (7.9) and multiple fold decrease in VEGF expression in LSD (-6.3), SSD (-5.1) and HSD (-14.1) compared to control. Activity of superoxide dismutase (SOD) and concentration of nitric oxide rose in LSD and SSD groups, and SSD and HSD groups respectively. Activities of glutathione peroxidase and catalase, and concentration of NADPH and hydrogen peroxide were not significantly different. IHC showed positive immunostaining for iNOS expression in all the groups while histopathology revealed moderate to severe prostatic hyperplasia in salt diet groups.

Conclusions

These findings suggest that low, standard and high salt diets aggravated the pathology of testosterone-induced BPH in Wistar rats by promoting inflammation, oxidative stress, while suppressing apoptosis and angiogenesis.
The effects of curcumin-piperine supplementation on inflammatory, oxidative stress and metabolic indices in patients with ischemic stroke in the rehabilitation phase: a randomized controlled trial
Authors: Boshagh Kosar , Khorvash Fariborz , Sahebkar Amirhossein , Majeed Muhammed , Bahreini Nimah , Askari Gholamreza , Bagherniya Mohammad
Published: December 2023

Background

Stroke is a leading cause of death worldwide, which is associated with a heavy economic and social burden. The purpose of this study was to investigate the effects of supplementation with curcumin-piperine combination in patients with ischemic stroke in the rehabilitation stage.

Methods

In this randomized controlled trial, 66 patients with stroke were randomized into two groups receiving curcumin-piperine tablets (500 mg curcumin + 5 mg piperine) and matched placebo tablets for 12 weeks. High-sensitivity C-reactive protein (hs-CRP), carotid intima-media thickness (CIMT), thrombosis, total antioxidant capacity (TAC), lipid profile, anthropometric indices, blood pressure, and quality of life were assessed before and after the intervention. Statistical data analysis was done using SPSS22 software.

Results

A total of 56 patients with a mean age of 59.80 ± 4.25 years completed the trial. Based on ANCOVA test, adjusted for baseline values, curcumin-piperine supplementation for 12 weeks resulted in significant reductions in serum levels of hs-CRP (p = 0.026), total cholesterol (TC) (p = 0.009), triglycerides (TG) (p = 0.001), CIMT (p = 0.002), weight (P = 0.001), waist circumference (p = 0.024), and systolic and diastolic blood pressure (p < 0.001), and a significant increase in TAC (p < 0.001) in comparison to the placebo. Pain score significantly increased in both groups; however, its increase was significantly higher in the placebo group compared with the intervention group (p = 0.007). No significant changes were observed between the two groups in terms of serum fibrinogen, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and quality of life indices.

Conclusion

Curcumin-piperine supplementation had beneficial effects on CIMT, serum hs-CRP, TC, TG, TAC, and systolic and diastolic blood pressure in patients with ischemic stroke in the rehabilitation stage.
Caprin-1 influences autophagy-induced tumor growth and immune modulation in pancreatic cancer
Authors: Yang Wenbo , Chen Hongze , Li Guanqun , Zhang Tao , Sui Yuhang , Liu Liwei , Hu Jisheng , Wang Gang , Chen Hua , Wang Yongwei , Li Xina , Tan Hongtao , Kong Rui , Sun Bei , Li Le
Published: December 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is characterized by rapid progression and poor prognosis. Understanding the genetic mechanisms that affect cancer properties and reprogram tumor immune microenvironment will develop new strategies to maximize the benefits for cancer therapies.

Methods

Gene signatures and biological processes associated with advanced cancer and unfavorable outcome were profiled using bulk RNA sequencing and spatial transcriptome sequencing, Caprin-1 was identified as an oncogenesis to expedite pancreatic cancer growth by activating autophagy. The mechanism of Caprin-1 inducing autophagy activation was further explored in vitro and in vivo. In addition, higher level of Caprin-1 was found to manipulate immune responses and inflammatory-related pathways. The immune profiles associated with increased levels of Caprin-1 were identified in human PDAC samples. The roles of CD4+T cells, CD8+T cells and tumor associated macrophages (TAMs) on clinical outcomes prediction were investigated.

Results

Caprin-1 was significantly upregulated in advanced PDAC and correlated with poor prognosis. Caprin-1 interacted with both ULK1 and STK38, and manipulated ULK1 phosphorylation which activated autophagy and exerted pro-tumorigenic phenotypes. Additionally, the infiltrated CD4+T cells and tumor associated macrophages (TAMs) were increased in Caprin-1High tissues. The extensive CD4+T cells determined poor clinical outcome in Caprin-1high patients, arguing that highly expressed Caprin-1 may assist cancer cells to escape from immune surveillance.

Conclusions

Our findings establish causal links between the upregulated expression of Caprin-1 and autophagy activation, which may manipulate immune responses in PDAC development. Our study provides insights into considering Caprin-1 as potential therapeutic target for PDAC treatment.
C3a/C3aR synergies with TGF-β to promote epithelial-mesenchymal transition of renal tubular epithelial cells via the activation of the NLRP3 inflammasome
Authors: You Danyu , Nie Kun , Wu Xiaoting , Weng Mengjie , Yang Liyan , Chen Yi , Cui Jiong , Wan Jianxin
Published: December 2023

Background

Complement component 3a and its receptor (C3a/C3aR) and the nucleotide-binding oligomerization domain-like receptor protein-3 (NLRP3) inflammasome contribute to epithelial-mesenchymal transition (EMT). However, the relationship between C3a/C3aR and the NLRP3 inflammasome in EMT remains unclear. This study aimed to elucidate the roles of C3a/C3aR and the NLRP3 inflammasome involved in TGF-β-induced EMT.

Method

Mouse renal tubular epithelial cells (TCMK-1) were exposed to C3a and TGF-β for 48 h. C3aR antagonist, MCC950, an inhibitor of the NLRP3 inflammasome and PD98059, an inhibitor of ERK signaling, were respectively applied to pretreat the cells at 30 min before C3a and TGF-β administration.The cells were collected for western blot, immunofluorescence staining and ELISA. Unilateral ureteral obstruction (UUO) models were established using male C57BL/6 wild-type (WT) mice and age-matched C3aR-deficient mice. MCC950 was intraperitoneally injected in UUO mice. Kidney samples were collected for immunohistochemistry staining.

Results

In vitro, C3a synergized with TGF-β to promote EMT and the activation of the NLRP3 inflammasome. Inhibition of C3aR attenuated EMT and the activation of the NLRP3 inflammasome. Inhibition of the NLRP3 inflammasome alleviated EMT but didn’t affect the expression of C3aR. Inhibition of ERK signaling inhibited the activation of the NLRP3 inflammasome. In vivo, the expression of IL-1β was significantly higher in UUO mice compared to the sham-operated mice. C3aR deficiency and inhibition of the NLRP3 Inflammasome contributed to decreased IL-1β in UUO mice.

Conclusion

Our data revealed that C3a/C3aR synergies with TGF-β to activate the NLRP3 inflammasome to promote epithelial-mesenchymal transition of renal tubular epithelial cells through ERK signaling, and the way in which C3aR activates the inflammasome is to promote the assembly of the NLRP3 inflammasome.
Role of IL-33-ST2 pathway in regulating inflammation: current evidence and future perspectives
Authors: Zhou Yilu , Xu Zhendong , Liu Zhiqiang
Published: December 2023

Interleukin (IL)-33 is an alarmin of the IL-1 superfamily localized to the nucleus of expressing cells, such as endothelial cells, epithelial cells, and fibroblasts. In response to cellular damage or stress, IL-33 is released and activates innate immune responses in some immune and structural cells via its receptor interleukin-1 receptor like-1 (IL-1RL1 or ST2). Recently, IL-33 has become a hot topic of research because of its role in pulmonary inflammation. The IL-33-ST2 signaling pathway plays a pro-inflammatory role by activating the type 2 inflammatory response, producing type 2 cytokines and chemokines. Elevated levels of IL-33 and ST2 have been observed in chronic pulmonary obstructive disease (COPD). Notably, IL-33 is present in COPD induced by cigarette smoke or acute inflammations. The role of IL-33 in sepsis is becoming increasingly prominent, and understanding its significance in the treatment of sepsis associated with high mortality is critical. In addition to its pro-inflammatory effects, the IL-33-ST2 axis appears to play a role in bacterial clearance and tissue repair. In this review, we focused on the role of the IL-33-ST2 axis in sepsis, asthma, and COPD and summarized the therapeutic targets associated with this axis, providing a basis for future treatment.
Addressing HIV stigma in healthcare, community, and legislative settings in Central and Eastern Europe
Authors: Schweitzer Ana-Maria , Dišković Arian , Krongauz Veronica , Newman Julie , Tomažič Janez , Yancheva Nina
Published: December 2023

Introduction

Surging HIV prevalence across countries of Central and Eastern Europe (CEE) is largely a result of poor HIV care engagement and a lack of comprehensive support for key populations. This is fostered by widespread stigma across healthcare, community, and legislative settings.

Discussion

Throughout CEE, HIV stigma and intersectional stigma are serious obstacles to providing adequate medical care to people living with HIV. Anticipated and enacted (experienced) stigma from healthcare professionals, and fears of breaches in confidentiality, deter individuals from having an HIV test and engaging in HIV care. Furthermore, negative connotations surrounding HIV infection can lead to discrimination from family, friends, colleagues, and the public, leading to internalized stigma and depression. Key populations that have higher HIV prevalence, such as men who have sex with men, people who inject drugs, transgender individuals, and sex workers, experience additional stigma and discrimination based on their behaviour and identities. This contributes to the concentrated HIV epidemics seen in these populations in many CEE countries. The stigma is exacerbated by punitive legislation that criminalizes HIV transmission and penalizes sexual orientation, drug use, gender identities, and sex work. Despite high levels of HIV stigma and intersectional stigma, there are many evidence-based interventions that have reduced stigma in other parts of the world. Here, we discuss the interventions that are currently being enacted in various countries of CEE, and we suggest additional effective, evidence-based interventions that will tackle stigma and lead to increased HIV care engagement and higher rates of viral suppression. We cover the promotion of the undetectable = untransmittable (U = U) message, stigma-reduction education and training for healthcare professionals, patient-centric approaches for testing and treatment, and advocacy for non-discriminatory legislation, policies, and practices. We also consider targeted stigma-reduction interventions that acknowledge the wider challenges faced by marginalized populations.

Conclusions

HIV stigma and intersectional stigma in CEE drive poor engagement with HIV testing services and care. Widespread adoption of evidence-based interventions to tackle stigma highlighted in this review will improve the quality of life of people living with HIV, improve HIV care engagement, and ultimately slow the surging HIV prevalence and concentrated epidemics occurring throughout CEE.
Effect of different types of Tai Chi exercise programs on the rate of change in bone mineral density in middle-aged adults at risk of osteoporosis: a randomized controlled trial
Authors: Kong Jianda , Tian Chunlan , Zhu Lei
Published: December 2023

Objective

To evaluate three Tai Chi (TC) exercise programs as intervention measures to compare their effects on improving rate of change in bone mineral density (BMD) in elderly individuals with osteoporosis (OP) and to propose the optimal exercise duration.

Methods

A randomized controlled trial (RCT) was conducted to identify study participants based on inclusion and exclusion criteria. Due to subject attrition, the number of participants analyzed decreased from 60 to 49. These participants were divided into four groups: 24-style TC Chuan group (24TCCG) (n = 13, 7 males/6 females), TC Kung Fu Fan group (TCKFFG) (n = 12, 5 males/7 females), TC Softball group (TCSBG) (n = 11, 6 males/5 females), and a control group (CG) (n = 13, 6 males/7 females). Except for the control group, each group received different TC exercise programs four times a week for 60 min per session, lasting for 16 weeks. BMD was measured using dual-energy X-ray absorptiometry (DXA) at the L2-L4 lumbar vertebrae, Ward's triangle, femoral neck, and greater trochanter. The rate of change of BMD was calculated using the formula.

Results

Compared with CG, all three TC groups showed significant improvements in BMD changes (P < 0.05), but their effects on the improvement of femoral neck and greater tuberosity BMD change rates were similar (P > 0.05). In addition, compared to the other exercise regimens, 24TCCG demonstrated more significant improvements in BMD at the L2-L4 lumbar vertebrae region and exhibited a more pronounced improvement in Ward's triangle BMD after only 8 weeks (P < 0.05). Short-term (≤ 4 weeks) TCKFFG was more effective than TCSBG in enhancing femoral neck BMD (P < 0.05). However, statistical significance was not found (P > 0.05) in all other cases.

Conclusion

These three TC exercise programs have similar positive effects on the BMD of the femoral neck and greater trochanter. However, compared with other exercise schemes, 24TCC showed a more significant improvement in BMD of the L2-L4 lumbar vertebrae region after just 8 weeks, as well as a more pronounced improvement in BMD of Ward's triangle. In terms of improving femoral neck BMD, TCKFF was found to be more effective than TCSB in less than 4 weeks. This study provides evidence for the effectiveness of TC exercise in improving BMD and preventing OP in the middle-aged and elderly high-risk population.
Prevention and treatment of osteoporosis with natural products: Regulatory mechanism based on cell ferroptosis
Authors: Yang Yunshang , Jiang Yifan , Qian Daoyi , Wang Zhirong , Xiao Long
Published: December 2023

Context

With the development of society, the number of patients with osteoporosis is increasing. The prevention and control of osteoporosis has become a serious and urgent issue. With the continuous progress of biomedical research, ferroptosis has attracted increased attention. However, the pathophysiology and mechanisms of ferroptosis and osteoporosis still need further study. Natural products are widely used in East Asian countries for osteoporosis prevention and treatment.

Objective

In this paper, we will discuss the basic mechanisms of ferroptosis, the relationship between ferroptosis and osteoclasts and osteoblasts, and in vitro and in vivo studies of natural products to prevent osteoporosis by interfering with ferroptosis.

Methods

This article takes ferroptosis, natural products, osteoporosis, osteoblasts and osteoclast as key words. Retrieve literature from 2012 to 2023 indexed in databases such as PubMed Central, PubMed, Web of Science, Scopus and ISI.

Results

Ferroptosis has many regulatory mechanisms, including the system XC -/GSH/GPX4, p62/Keap1/Nrf2, FSP1/NAD (P) H/CoQ10, P53/SAT1/ALOX15 axes etc. Interestingly, we found that natural products, such as Artemisinin, Biochanin A and Quercetin, can play a role in treating osteoporosis by promoting ferroptosis of osteoclast and inhibiting ferroptosis of osteoblasts.

Conclusions

Natural products have great potential to regulate OBs and OCs by mediating ferroptosis to prevent and treat osteoporosis, and it is worthwhile to explore and discover more natural products that can prevent and treat osteoporosis.
Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA
Authors: Hu Pan , Zhou Peiyi , Sun Tieyun , Liu Dingkang , Yin Jun , Liu Lubin
Published: December 2023

Triple-negative breast cancer (TNBC) represents the most challenging subtype of breast cancer. Studies have implicated an upregulation of lipid synthesis pathways in the initiation and progression of TNBC. Targeting lipid synthesis pathways may be a promising therapeutic strategy for TNBC. Our previous study developed a therapeutic protein PAK with passive targeting and inhibiting tumor proliferation. In this study, we further substantiate the efficacy of PAK in TNBC. Transcriptome sequencing analysis revealed PAK-mediated downregulation of genes involved in fatty acid synthesis, including key genes like SREBP-1, FASN, and SCD1. RNA immunoprecipitation experiments demonstrated a significant binding affinity of PAK to SREBP-1 mRNA, facilitating its degradation process. Both in vitro and in vivo models, PAK hampered TNBC progression by downregulating lipid synthesis pathways. In conclusion, this study emphasizes that PAK inhibits the progression of TNBC by binding to and degrading SREBP-1 mRNA, revealing a new strategy for regulating lipid synthesis in the intervention of TNBC and its therapeutic significance.
Challenges regarding informed consent in recruitment to clinical research: a qualitative study of clinical research nurses’ experiences
Authors: Godskesen Tove , Björk Joar , Juth Niklas
Published: December 2023

Background

Clinical research nurses (CRNs) have first-hand experience with ethical challenges and play a crucial role in upholding ethical conduct and adherence to the principles of informed consent in clinical research. This study explores the ethical challenges encountered by CRNs in the process of obtaining informed consent for clinical research.

Methods

A qualitative exploratory design. Semistructured interviews (n = 14) were conducted with diverse CRNs in Sweden. These CRNs covered a wide range of research fields, including pharmaceutical and academic studies, interventions, and observational research, spanning different trial phases, patient categories, and medical conditions. The interviews were analysed using inductive qualitative content analysis.

Results

The analysis identified three main categories: (i) threats to voluntariness, (ii) measures to safeguard voluntariness, and (iii) questionable exclusion of certain groups. CRNs face challenges due to time constraints, rushed decisions, information overload, and excessive reliance on physicians’ recommendations. Overestimating therapeutic benefits in stages of advanced illness emerged as a risk to voluntariness. CRNs outlined proactive solutions, such as allowing ample decision-making time and offering support, especially for terminally ill patients. Concerns were also voiced about excluding certain demographics, such as those with language barriers or cognitive impairments.

Conclusions

In conclusion, upholding ethical research standards requires recognising various factors affecting patient voluntariness. Researchers and CRNs should prioritise refining the informed consent process, overcoming participation challenges, and aligning scientific rigour with personalised care. Additionally, a concerted effort is vital to meet the diverse needs of patient populations, including equitable inclusion of individuals with language barriers or cognitive limitations in clinical studies. These findings have significant implications for enhancing the ethics of clinical research and advancing person-centred care.
Acute ischemia induces spatially and transcriptionally distinct microglial subclusters
Authors: Li Huiya , Liu Pinyi , Zhang Bing , Yuan Zengqiang , Guo Mengdi , Zou Xinxin , Qian Yi , Deng Shiji , Zhu Liwen , Cao Xiang , Tao Tao , Xia Shengnan , Bao Xinyu , Xu Yun
Published: December 2023

Background

Damage in the ischemic core and penumbra after stroke affects patient prognosis. Microglia immediately respond to ischemic insult and initiate immune inflammation, playing an important role in the cellular injury after stroke. However, the microglial heterogeneity and the mechanisms involved remain unclear.

Methods

We first performed single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST) on middle cerebral artery occlusion (MCAO) mice from three time points to determine stroke-associated microglial subclusters and their spatial distributions. Furthermore, the expression of microglial subcluster-specific marker genes and the localization of different microglial subclusters were verified on MCAO mice through RNAscope and immunofluorescence. Gene set variation analysis (GSVA) was performed to reveal functional characteristics of microglia sub-clusters. Additionally, ingenuity pathway analysis (IPA) was used to explore upstream regulators of microglial subclusters, which was confirmed by immunofluorescence, RT-qPCR, shRNA-mediated knockdown, and targeted metabolomics. Finally, the infarct size, neurological deficits, and neuronal apoptosis were evaluated in MCAO mice after manipulation of specific microglial subcluster.

Results

We discovered stroke-associated microglial subclusters in the brains of MCAO mice. We also identified novel marker genes of these microglial subclusters and defined these cells as ischemic core-associated (ICAM) and ischemic penumbra-associated (IPAM) microglia, according to their spatial distribution. ICAM, induced by damage-associated molecular patterns, are probably fueled by glycolysis, and exhibit increased pro-inflammatory cytokines and chemokines production. BACH1 is a key transcription factor driving ICAM generation. In contrast, glucocorticoids, which are enriched in the penumbra, likely trigger IPAM formation, which are presumably powered by the citrate cycle and oxidative phosphorylation and are characterized by moderate pro-inflammatory responses, inflammation-alleviating metabolic features, and myelinotrophic properties.

Conclusions

ICAM could induce excessive neuroinflammation, aggravating brain injury, whereas IPAM probably exhibit neuroprotective features, which could be essential for the homeostasis and survival of cells in the penumbra. Our findings provide a biological basis for targeting specific microglial subclusters as a potential therapeutic strategy for ischemic stroke.
Patient outcomes associated with subcutaneous C1INH prophylaxis for hereditary angioedema: a retrospective analysis
Authors: Lumry William , Craig Timothy , Anderson John , Riedl Marc , Li Henry , Tachdjian Raffi , Manning Michael , Bajcic Paolo , Rodino Frank , Wang Sam , Sexton Thomas R. , Bernstein Jonathan A.
Published: December 2023

Background

Real-world data on subcutaneous C1INH (C1INH[SC]) usage and patient-level impacts on hereditary angioedema (HAE)-related outcomes and quality of life (QoL) are both lacking and challenging to generate using conventional study methodologies. Using a hybrid study design involving patient interviews supplemented by retrospective medical chart data review, we conducted a real-world assessment of the impact of C1INH(SC) prophylaxis on HAE attack patterns, QoL, and on-demand medication use.

Methods

The study was conducted at seven US sites and included 36 adults with HAE who had been treated with C1INH(SC) long-term prophylaxis following ≥ 12 months of on-demand management only. Patients underwent 30-min interviews, facilitated and analyzed by a trained qualitative research specialist. Medical records were reviewed for 12 months before (pre-index) and after (post-index) initiation of C1INH(SC). Using interview data with descriptive terms converted to numerical values, we compared pre- versus post-index attack frequency, severity, and rescue medication usage.

Results

Mean (SD) annualized attack frequency per patient decreased 82.0%, from 38.8 (38.8) attacks/year pre-index to 7.0 (15.3) attacks/year (P < 0.001); the median number of attacks decreased by 97.0% (30 pre-index to 1 post-index). For 20 patients, the annualized attack rate after starting C1INH(SC) prophylaxis was ≤ 1 attack/year; 12 of these patients reported 0 attacks. Mean (SD) attack severity (scale: 0 = none/mild to 4 = very severe) decreased from 2.3 (0.7) pre-index to 0.9 (0.9) post-index (P < 0.001). Mean/median rescue medication use decreased by 77.2%/96.3%. Improved QoL was narratively described for many domains.

Conclusions

These real-world findings indicate that long-term prophylaxis with C1INH(SC) markedly improves important factors that contribute to the goal of achieving total disease control and normalization of patients’ lives, including fewer and less severe attacks, less rescue medication usage, and improved QoL.
Single-stage bilateral conversion arthroplasty for hip fusion via direct anterior approach in a patient with severe ankylosing spondylitis and kyphoscoliosis: a case report
Authors: Beheshti Fard Shahabaldin , Afzal Sina , Barzegar Mohammadreza , Mortazavi Seyed Mohammad Javad
Published: December 2023

Background

Severe ankylosing spondylitis (AS) frequently involves hip joints and, occasionally, presents with concurrent spinal deformities, such as kyphoscoliosis, creating complex challenges for surgical management.

Case presentation

We present a 26-year-old Persian male with a history of AS and severe kyphoscoliosis, leading to bilateral hip fusion and immobility. Following spinal deformity correction, a one-stage bilateral conversion to total hip arthroplasty (THA) was conducted through the direct anterior approach.

Conclusion

Primary correction of spinal deformities allows for extended surgical procedures under general anesthesia. Single stage bilateral hip conversion arthroplasty via the direct anterior approach enhances postoperative mobilization, reduce the risk of re-ankylosis, and improve the overall quality of life for AS patients with this unique presentation.
A new self-adaptive method for solving resolvent of sum of two monotone operators in Banach spaces
Authors: Abass H. A. , Aphane M. , Oyewole O. K.
Published: December 2023

We introduce a Tseng extragradient method for solving monotone inclusion problem in Banach space. A strong convergence result of an Halpern inertial extrapolation method for solving the resolvent of sum of two monotone operators without the knowledge of the Lipschitz constant was established. Lastly, we illustrate some numerical behavior of our iterative scheme to showcase the performance of the proposed method compared to other related results in the literature.
What kind of illness is anorexia nervosa? Revisited: some preliminary thoughts to finding a cure
Authors: Touyz S. , Bryant E. , Dann K. M. , Polivy J. , Le Grange D. , Hay P. , Lacey H. , Aouad P. , Barakat S. , Miskovic-Wheatley J. , Griffiths K. , Carroll B. , Calvert S. , Maguire S.
Published: December 2023

Two decades have elapsed since our publication of ‘What kind of illness is anorexia nervosa?’. The question remains whether our understanding of anorexia nervosa and its treatment thereof has evolved over this time. The verdict is disappointing at best. Our current gold standard treatments remain over-valued and clinical outcomes are modest at best. Those in our field are haunted by the constant reminder that anorexia nervosa carries the highest mortality rate of any psychiatric disorder. This cannot continue and demands immediate action. In this essay, we tackle the myths that bedevil our field and explore a deeper phenotyping of anorexia nervosa. We argue that we can no longer declare agnostic views of the disorder or conceive treatments that are “brainless”: it is incumbent upon us to challenge the prevailing zeitgeist and reconceptualise anorexia nervosa. Here we provide a roadmap for the future.
Buried bumper syndrome in percutaneous endoscopic gastrostomy with a jejunal extension tube in patients undergoing levodopa–carbidopa intestinal gel treatment
Authors: Nakagawa Masatoshi , Inoue Noboru , Takise Shuhei , Takayanagi Masashi , Kubo Tsukasa , Muroi Hiroto , Nakajima Masanobu , Morita Shinji , Nakamura Takatoshi , Kojima Kazuyuki
Published: December 2023

Background

Levodopa–carbidopa intestinal gel (LCIG) treatment is an effective Parkinson’s disease (PD) treatment that requires percutaneous endoscopic gastrostomy with a jejunal extension tube (PEG-J). Buried bumper syndrome (BBS) is an uncommon but significant complication of PEG-J for LCIG.

Case presentation

A 71-year-old man had been undergoing LCIG therapy for PD since a PEG-J was implemented at our department two years previously. He presented with appetite loss. Computed tomography showed that the gastrostomy bumper was buried in the gastric wall. The patient was surgically treated with the simultaneous removal and replacement of PEG-J. Postoperative gastrocutaneous fistula occurred, which was conservatively treated.

Conclusions

Notably, patients and medical staff should be aware that patients with PD on LCIG treatment have a high risk of BBS in PEG-J and that there might be some patients with latent BBS. When simultaneous removal and replacement surgery is performed, establishing a new route at the stomach and abdominal wall is recommended.
Patterns of mental health service use among perpetrators of domestic homicide: descriptive study of Domestic Homicide Reviews in England and Wales
Authors: MacInnes Poppy , Calcia Marilia A. , Martinuzzi Michela , Griffin Cora , Oram Siân , Howard Louise M.
Published: December 2023

Aims and method

We used data from Domestic Homicide Reviews (DHRs) to describe the patterns of mental health service use by perpetrators of domestic homicide in England and Wales. In 186 DHR reports we compared the characteristics of perpetrators who accessed mental health services with those of perpetrators who did not. Separate analyses were conducted for perpetrators of intimate partner homicide (IPH) and family homicide.

Results

Over two-thirds (64.5%, n = 120) of the perpetrators had accessed mental healthcare before the homicide. Perpetrators of IPH who had used mental health services compared with those who had not were more likely to have a history of substance misuse, contact with the criminal justice system and a history of self-harm or suicide attempts.

Clinical implications

Our findings support the need for health services, particularly mental health, addictions and primary care, to take an assertive role in the prevention of domestic violence and abuse by identifying patients who are potential perpetrators of domestic violence and abuse.
In situ regeneration of inner hair cells in the damaged cochlea by temporally regulated co-expression of Atoh1 and Tbx2
Authors: Li Xiang , Ren Minhui , Gu Yunpeng , Zhu Tong , Zhang Yu , Li Jie , Li Chao , Wang Guangqin , Song Lei , Bi Zhenghong , Liu Zhiyong
Published: December 2023

Cochlear inner hair cells (IHCs) are primary sound receptors, and are therefore a target for developing treatments for hearing impairment. IHC regeneration in vivo has been widely attempted, although not yet in the IHC-damaged cochlea. Moreover, the extent to which new IHCs resemble wild-type IHCs remains unclear, as is the ability of new IHCs to improve hearing. Here, we have developed an in vivo mouse model wherein wild-type IHCs were pre-damaged and nonsensory supporting cells were transformed into IHCs by ectopically expressing Atoh1 transiently and Tbx2 permanently. Notably, the new IHCs expressed the functional marker vGlut3 and presented similar transcriptomic and electrophysiological properties to wild-type IHCs. Furthermore, the formation efficiency and maturity of new IHCs were higher than those previously reported, although marked hearing improvement was not achieved, at least partly due to defective mechanoelectrical transduction (MET) in new IHCs. Thus, we have successfully regenerated new IHCs resembling wild-type IHCs in many respects in the damaged cochlea. Our findings suggest that the defective MET is a critical barrier that prevents the restoration of hearing capacity and should thus facilitate future IHC regeneration studies.
Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to Five Years after Diagnosis
Authors: Smit Karel C. , Derksen Jeroen W.G. , Stellato Rebecca K. , van Lanen Anne-Sophie , Wesselink Evertine , Belt Eric J. Th. , Cloos-van Balen Marissa , Coene Peter Paul L.O. , Dekker Jan Willem T. , de Groot Jan Willem , Haringhuizen Annebeth W. , van Halteren Henk K. , van Heek Tjarda T. , Helgason Helgi H. , Hendriks Mathijs P. , de Hingh Ignace H.J.T. , Hoekstra Ronald , Houtsma Danny , Janssen Johan J.B. , Kok Niels , Konsten Joop L.M. , Los Maartje , Meijerink Martijn R. , Mekenkamp Leonie J.M. , Peeters Koen C.M.J. , Polée Marco B. , Rietbroek Ron C. , Schiphorst Anandi H.W. , Schrauwen Ruud W.M. , Schreinemakers Jennifer , Sie Mark P.S. , Simkens Lieke , Sonneveld Eric J.A. , Terheggen Frederiek , Valkenburg-van Iersel Liselot , Vles Wouter J. , Wasowicz-Kemps Daria K. , de Wilt Johannes H.W. , Kok Dieuwertje E. , Winkels Renate M. , Kampman Ellen , van Duijnhoven Fränzel J.B. , Koopman Miriam , May Anne M.
Published: December 2023

Introduction

Physical activity (PA) is associated with higher quality of life and probably better prognosis among colorectal cancer (CRC) patients. This study focuses on determinants of PA among CRC patients from diagnosis until five years post-diagnosis.

Methods

Sociodemographic and disease-related factors of participants of two large CRC cohort studies were combined. Moderate-to-vigorous PA during sport and leisure time (MVPA-SL) was measured at diagnosis (T0) and six, twelve, twenty-four, and sixty (T6 to T60) months post-diagnosis, using the SQUASH questionnaire. Mixed-effects models were performed to identify sociodemographic and disease-related determinants of MVPA-SL, separately for stage I-III colon (CC), stage I-III rectal cancer (RC), and stage IV CRC (T0 and T6 only). Associations were defined as consistently present when significant at ≥4 timepoints for the stage I-III subsets. MVPA-SL levels were compared with an age- and sex-matched sample of the general Dutch population.

Results

In total, 2905 CC, 1459 RC and 436 stage IV CRC patients were included. Patients with higher fatigue scores, and women compared to men had consistently lower MVPA-SL levels over time, regardless of tumor type and stage. At T6, having a stoma was significantly associated with lower MVPA-SL among stage I-III RC patients. Systemic therapy and radiotherapy were not significantly associated with MVPA-SL changes at T6. Compared to the general population, MVPA-SL levels of CRC patients were lower at all timepoints, most notably at T6.

Conclusions

Female sex and higher fatigue scores were consistent determinants of lower MVPA-SL levels among all CRC patients, and MVPA-SL levels were lowest at six months post-diagnosis. Our results can inform the design of intervention studies aimed at improving PA, and guide healthcare professionals in optimizing individualized support.
Improvements in Orthostatic Tolerance with Exercise Are Augmented by Heat Acclimation: A Randomised Controlled Trial
Authors: Parsons Iain T. , Snape Daniel , Stacey Michael J. , Barlow Matthew , O’Hara John , Gall Nick , Chowienczyk Phil , Wainwright Barney , Woods David R
Published: December 2023

Introduction

Heat adaptation is protective against heat illness however its role in heat syncope, due to reflex mechanisms, has not been conclusively established. The aim of this study was to evaluate if heat acclimation (HA) was protective against heat syncope and to ascertain underlying physiological mechanisms.

Methods

20 (15 males, 5 females) endurance trained athletes were randomised to either 8 days of mixed active and passive HA (HEAT) or climatically temperate exercise (CONTROL). Prior to, and following, the interventions participants underwent a head up tilt (HUT) with graded lower body negative pressure (LBNP), in a thermal chamber (32.0 ± 0.3 °C), continued until presyncope with measurement of cardiovascular parameters. Heat stress tests (HST) were performed to determine physiological and perceptual measures of HA.

Results

There was a significant increase in orthostatic tolerance (OT), as measured by HUT/LBNP, in the HEAT group (pre-intervention; 28 ± 9 mins, post-intervention; 40 ± 7 mins) compared to CONTROL (pre-intervention; 30 ± 8 mins, post-intervention; 33 ± 5 mins) (p = 0.01). HA resulted in a significantly reduced peak and mean rectal and skin temperature (p < 0.01), peak heat rate (p < 0.003), thermal comfort (p < 0.04) and rating of perceived exertion (p < 0.02) during HST. There was a significantly increased plasma volume (PV) in the HEAT group in comparison to CONTROL (p = 0.03).

Conclusions

HA causes improvements in OT and is likely to be beneficial in patients with heat exacerbated reflex syncope. HA mediated PV expansion is a potential physiological mechanism underlying improved OT.
Κατανόηση των φυσικών επιστημών από το ευρύ κοινό
Authors: Χούπη Μαρία
Published: December 2023

Η έλλειψη ενδιαφέροντος των νέων για τις Φυσικές Επιστήμες (Φ.Ε.) γενικά και τη Φυσική ειδικότερα έχει αναγνωριστεί τα τελευταία χρόνια σε παγκόσμια κλίμακα. Τόσο η πολιτική ηγεσία της Ευρωπαϊκής Ένωσης (Ε.Ε.) όσο και η εκπαιδευτική κοινότητα αναγνωρίζει ως βασικό πρόβλημα αυτής της κατάστασης στον τρόπο διδασκαλίας των Φ.Ε. Η Ε.Ε. θεωρεί τις Φ.Ε. βασικό πυλώνα της οικονομικής της ανάπτυξης και ευημερίας. Διατίθενται οικονομικοί πόροι και δοκιμάζονται νέες μέθοδοι διδασκαλίας, με πενιχρά αποτελέσματα. Η Δημόσια Κατανόηση της Επιστήμης και ο Επιστημονικός Εγγραμματισμός, δύο συγγενείς μεταξύ τους έννοιες, αποτελούν βασικούς στόχους της παγκόσμιας κοινότητας. Την περίοδο της πανδημίας covid-19 φάνηκε η αδυναμία του ευρέως κοινού να κρίνει, να επιλέξει και να εφαρμόσει βασικές επιστημονικές αρχές στην καθημερινή του ζωή. Η εκ-παίδευση των Φ.Ε. οφείλει να παίξει σημαντικό ρόλο και σε αυτούς τους τομείς. Το περιεχόμενο του Αναλυτικού Προγράμματος Σπουδών (ΑΠΣ) Φυσικής δύναται να αποτελέσει βασικό παράγοντα μεταστροφής της κατάστασης. Στην παρούσα διατριβή διερευνώνται οι στάσεις και οι αντιλήψεις/πεποιθήσεις των μαθητών/τριών διαφορετικών τύπων σχολείων Δευτεροβάθμιας Εκπαίδευσης από τρεις περιοχές της Ελλάδας. Από την ανάλυση των ερωτήσεων προέκυψε ότι οι μαθητές/τριες θεωρούν τη Φυσική δυσνόητο και δύσκολο μάθημα κυρίως λόγω των πολλών και δύσκολων ασκήσεων αλλά ενδιαφέρον και ίσως χρήσιμο για τη μετέπειτα ζωή τους. Εντοπίστηκαν διαφορές στις στάσεις ως προς το φύλο, ως προς τον τύπο της σχολικής μονάδας, το κοινωνικο-οικονομικό επίπεδο της σχολικής μονάδας και το βαθμό αστικοποίησης της σχολικής μονάδας. Προέκυψε ότι η εκπαιδευτική διαδικασία δεν καταφέρνει να αμβλύνει τις αρνητικές στάσεις των μαθητών/τριών αλλά αμβλύνει σε μικρό βαθμό τις πεποιθήσεις τους. Οι μαθητές/τριες αποδίδουν στο εκπαιδευτικό σύστημα και στο σχολικό περιβάλλον το μειωμένο ενδιαφέρον τους στη Φυσική. Τονίζουν το σπουδαίο ρόλο που παίζει η διδακτική διαδικασία, το σχολείο, οι διδακτικές μέθοδοι και ο εκπαιδευτικός στην προσέλκυση του ενδιαφέροντος. Από τη σύγκριση των εφαρμοζόμενων πολιτικών στα νέα ΑΠΣ με τα αποτελέσματα της μελέτης μας προέκυψε ότι, σε θεωρητικό τουλάχιστον επίπεδο, έχουν ενσωματωθεί στα νέα ΑΠΣ αρκετά στοιχεία από τις απόψεις των μαθητών/τριών έτσι όπως εκφράστηκαν στην έρευνά μας.
Law enforcement agencies
Authors: Chernyavskiy Aleksandr , Zotov Anatoliy , Voroncova Sof'ya
Published: December 2023

The textbook examines the main directions of organizing the activities of law enforcement agencies in Russia, highlights the activities of the judiciary and justice, crime detection and investigation bodies, the prosecutor's office, justice and security, as well as the bar, notary, the legal status of judges, prosecutors, etc. The latest legislative changes are reflected, the modern system of law enforcement agencies in Russia and some foreign countries is revealed.
Meets the requirements of the federal state educational standards of secondary vocational education of the latest generation.
For students of secondary vocational education institutions, as well as anyone interested in the system of law enforcement agencies of the Russian Federation.