bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome analysis revealed gene expression feminization of testis after exogenous tetrodotoxin administration in pufferfish Takifugu flavidus
Authors: He Xue , Wu Hexing , Ye Yaping , Gong Xiaolin , Bao Baolong
Published: August 2022

Tetrodotoxin (TTX) is a deadly neurotoxin and usually accumulates in large amounts in the ovaries but is non-toxic or low toxic in the testis of pufferfish. The molecular mechanism underlying sexual dimorphism accumulation of TTX in ovary and testis, and the relationship between TTX accumulation with sex related genes expression remain largely unknown. The present study investigated the effects of exogenous TTX treatment on Takifugu flavidus. The results demonstrated that exogenous TTX administration significantly incresed level of TTX concentration in kidney, cholecyst, skin, liver, heart, muscle, ovary and testis of the treatment group (TG) than that of the control group (CG). Transcriptome sequencing and analysis were performed to study differential expression profiles of mRNA and piRNA after TTX administration of the ovary and testis. The results showed that compared with female control group (FCG) and male control group (MCG), TTX administration resulted in 80 and 23 piRNAs, 126 and 223 genes up and down regulated expression in female TTX-treated group (FTG), meanwhile, 286 and 223 piRNAs, 2 and 443 genes up and down regulated expression in male TTX-treated group (MTG). The female dominant genes cyp19a1, gdf9 and foxl2 were found to be up-regulated in MTG. The cyp19a1, whose corresponding target piRNA uniq_554482 was identified as down-regulated in the MTG, indicating the gene expression feminization in testis after exogenous TTX administration. The KEGG enrichment analysis revealed that differentially expressed genes (DEGs) and piRNAs (DEpiRNAs) in MTG vs MCG group were more enriched in metabolism pathways, indicating that the testis produced more metabolic pathways in response to exogenous TTX, which might be a reason for the sexual dimorphism of TTX distribution in gonads. In addition, TdT-mediated dUTP-biotin nick end labeling staining showed that significant apoptosis was detected in the MTG testis, and the role of the cell apoptotic pathways was further confirmed. Overall, our research revealed that the response of the ovary and testis to TTX administration was largely different, the ovary is more tolerant whereas the testis is more sensitive to TTX. These data will deepen our understanding on the accumulation of TTX sexual dimorphism in Takifugu.
Safety and effectiveness of a novel dielectric mapping system: one-year, two chinese centers experiences
Authors: Ding Lei , Huang Xiao , Dai Cong , Zhang Hongda , Weng Sixian , Yu Fengyuan , Qi Yingjie , Zhang Shu , Shi Ruizheng , Tang Min
Published: August 2022

Background

The KODEX-EPD system is a novel, dielectric three-dimensional mapping system. We aim to illustrate the feasibility, safety, and outcomes of ablation using the KODEX-EPD system.

Methods

A total of 272 patients with supraventricular arrhythmias were enrolled and underwent catheter ablation using the KODEX-EPD system from October 2020 to July 2021. The feasibility, safety, and ablation outcomes were analyzed.

Results

Of the enrolled patients, 15 (5.4%) had atrial tachycardia (AT), 88 (31.4%) had atrioventricular reentrant tachycardia (AVRT), 141 (50.4%) had atrioventricular nodal reentrant tachycardia (AVNRT), 34 (12.1%) had atrial fibrillation (AF), and 9 (3.2%) had atrial flutter (AFL). All AF patients included were first-do-pulmonary vein isolation (PVI); there were 26 paroxysmal AF and 8 persistent AF. All patients achieved immediate success of ablation. The mean follow-up duration was 11.8 ± 2.4 months. One patient (1.1%) in the AVRT subgroup and two patients (1.4%) in the AVNRT subgroup experienced recurrence. When considering a three-month blanking time, the estimated freedom of AF at one-year post-ablation with and without AADs was 75.7% and 70.4%, respectively. The Kaplan–Meier analysis showed no significant difference in the overall AF recurrence (log-rank; P = 0.931) or AAD-free AF recurrence (log-rank; P = 0.841) between RFCA and cryoablation. One patient had mild pulmonary embolism. None of the patients died or had a cerebrovascular event in the periprocedural period.

Conclusions

This retrospective, two-center study demonstrated that catheter ablation of supraventricular arrhythmias using the KODEX-EPD system is feasible, safe, and effective.

Trial registration Retrospectively registered.
Low appendicular skeletal muscle mass index is associated with the anthropometric variables of post-menopausal women
Authors: da Cruz Geise Ferreira , Lunz Tatiana Mion , Rocha de Jesus Tatielle , Costa Mariana Braga , Vidigal Camila Vilarinho , Albergaria Ben-Hur , Marques-Rocha José Luiz , Guandalini Valdete Regina
Published: August 2022

Background

Skeletal muscle mass is a central component of body composition and its decline is enhanced during aging. We verified the association between the appendicular skeletal muscle mass index (ASMI) with the anthropometric variables, biochemical variables, and lifestyle of postmenopausal women.

Methods

Cross-sectional observational study conducted with postmenopausal women. Sociodemographic, clinical, lifestyle, physical activity level, biochemical, and anthropometric markers were collected. Body composition was assessed by dual-energy densitometry. Multivariate logistic regression analysis was applied.

Results

One hundred fourteen women aged in average 66.0 ± 5.8 years were evaluated. There was a significant association between ASMI and age (p = 0.004), body mass (p < 0.001), body mass index (BMI) (p < 0.001), adductor pollicis muscle thickness (APMT) (p < 0.001), plasma calcium levels (p = 0.003), calf circumference (CC), and waist circumference (WC) (p < 0.001 for both). Adjusted regression analyses revealed the influence of BMI, CC, and APMT in the 1st tertile of ASMI (p < 0.05), BMI and CC in the 2rd tertile of ASMI.

Conclusions

ASMI was associated with BMI and muscle mass reserve indicators such as CC and DAPMT. In clinical practice, this indicates that simple, low-cost measures with good applicability can be used to predict and track the risk of depletion of skeletal muscle mass and consequent sarcopenia.
What is the postoperative nutrition intake in children with congenital heart disease? A single-center analysis in China
Authors: Ni Ping , Zhang Mingjie , Wu Yibei , Luo Wenyi , Xu Zhuoming
Published: August 2022

Background

It is common that inadequate nutritional intake happens in patients with congenital heart disease (CHD), which can adversely affect the prognosis of patients. However, the details and reasons are not clear enough so far. Therefore, the primary aim of this study was to investigate the current nutritional requirements and energy intake on days 1–7 in the cardiac intensive care unit after surgery. Our secondary aim was to investigate potential factors that hinder nutritional supply and to compare the resting energy expenditure (REE) based on two methods, the Fick method and the Schofield equation.

Methods

Using retrospective analysis, we collected data from postoperative children with CHD at a children's hospital in Shanghai, China. We used the Fick method to calculate the REE, and compare the results with the actual enteral nutrition intake. Meanwhile, we recorded the initiation time of enteral nutrition, feeding intolerance, unfinished milk volume, etc. Then the correlation between the results of the Fick method and the equation method was calculated.

Results

A total of 49 patients were included, with a median age of 22 months (IQR 4.9, 57.3), and a median Aristotle basic complexity score of 8 (IQR 6.0, 9.8). The time interval for surgical intervention within 7 days after operation was 4 (IQR 2.5, 6). No statistical difference in REE on postoperative days 1–7. The average enteral nutrition energy provided 64.6 (33.6, 79.6)% of the REE, which showed a significant decrease on postoperative day 4, and then reached its lowest on postoperative day 5. The protein supply was 0.7 ± 0.3 kcal/kg/d. In addition, the REE calculated by the Fick method was moderately correlated with that estimated by the equation (r = 0.467, P = 0.001).

Conclusions

The energy and protein supply in the acute postoperative period in children with CHD is inadequate. Fluid restriction and fasting may be the main causes. In addition, there is a moderate correlation between the REE calculated by the Fick method and that estimated by the equation.
Drowning in the Eastern Mediterranean region: a systematic literature review of the epidemiology, risk factors and strategies for prevention
Authors: Peden Amy E. , Işın Ali
Published: August 2022

Introduction

Globally, drowning is a significant cause of preventable mortality and morbidity. The Eastern Mediterranean region (EMR) comprises 22 countries of extreme disparity in income and is a region impacted by conflict and migration. We systematically review literature published on drowning in the EMR.

Methods

Peer-reviewed literature (limited to original research) was identified using Embase, PubMed, Scopus, SportsDiscus, and Web of Science databases. Literature was independently dual screened at title/abstract and full text stages with dual data extraction (20% of included studies). Studies were included if they reported epidemiology, risk/protective factors and/or prevention strategies for drowning (unintentional and intentional; fatal and non-fatal) of residents, tourists or migrants in the EMR. Literature was assessed against the [Australian] National Health and Medical Research Council’s Levels of Evidence.

Results

Seventy-two studies were included in this review (epidemiology 68 studies; risk/protective factor 13 studies; prevention strategies 19 studies). Iran (n = 27), Saudia Arabia (n = 11) and Pakistan (n = 10) recorded the largest number of dedicated studies. Studies predominately focused on unintentional drowning. Ninety-two percent of included studies (n = 66) were ranked as being low evidence (level IV). The majority of studies explored drowning among children and adolescents (0–19 years). All-age fatal drowning rates varied from a low of 0.48 per 100,000 (United Arab Emirates; 2002; Ministry of Health death registry data) to a high of 18.5 per 100,000 (Egypt; 2014–15; WHO mortality database). Commonly identified risk factors included being male, young age, submersion time and resident status. Common prevention strategies public education, lifeguard supervision, and cardiopulmonary resuscitation.

Discussion

Gaps in understanding of drowning burden in some countries within the region, as well as region-wide risk factor identification for adult drowning, intentional and migration-related drowning, impair the ability of nations to advance drowning prevention. There is a need for investment in implementation and evaluation of drowning prevention interventions in the EMR.

Conclusion

Drowning is a significant cause of mortality and morbidity in the EMR. The recent UN declaration on global drowning prevention may provide the impetus to invest in drowning prevention research, policy, and advocacy with the aim of reducing drowning-related harms in the EMR.

Trial registration

Registration number: #CRD42021271215.
Evaluation of the expression pattern and diagnostic value of PPARγ in malignant and benign primary bone tumors
Authors: Eghtedari Amir Reza , Vaezi Mohammad Amin , Safizadeh Banafsheh , Ghasempour Ghasem , Babaheidarian Pegah , Salimi Vahid , Tavakoli-Yaraki Masoumeh
Published: August 2022

Purpose

The quantifiable description of PPARγ expression pattern beside mechanistic in-vitro evidence will provide insights into the involvement of this mediator in tumor pathogenesis. This study is focused on illuminating the PPARγ gene and protein expression pattern, its association with tumor deterioration and its diagnostic value in different types of primary bone tumors.

Methods

The expression pattern of PPARγ was investigated in the 180 bone tissues including 90 bone tumor tissues and 90 non-cancerous bone tissues. The local PPARγ expression level was assessed using real-time qRT-PCR and the PPARγ protein expression pattern was measured using immunohistochemistry. The correlation of PPARγ expression level with patients’ clinic-pathological features, also the value of the variables in predicting PPARγ expression level in tumors and the value of PPARγ to discriminate tumor subtypes were assessed.

Results

The mean PPARγ mRNA expression was significantly higher in bone tumors compared to healthy bone tissues, also the malignant tumors including osteosarcoma and Ewing sarcoma had the elevated level of PPARγ mRNA compared to GCT tumors. Consistently, the protein expression of PPARγ in the tumor site was significantly higher in the bone tumors and malignant tumors compared to non-cancerous and benign tumors, respectively. The PPARγ protein could predict malignant tumor features including tumor grade, metastasis and recurrence significantly. Moreover, PPARγ could potentially discriminate the patients from the controls also malignant tumors from benign tumors with significant sensitivity and specificity.

Conclusions

PPARγ might be involved in primary bone tumor pathogenesis and determining its molecular mechanism regarding bone cancer pathogenesis is of grave importance.
Evaluation of a collaborative ambulatory orthopedic care program for patients with hip and knee osteoarthritis: a comparative observational cohort study
Authors: Müller Angelina , Amberger Olga A. , Glushan Anastasiya , Witte Claudia , Klaaßen-Mielke Renate , Lembeck Burkhard , Beyer Martin , Gerlach Ferdinand M. , Karimova Kateryna
Published: August 2022

Background

In 2014, the novel orthopedic care program was established by the AOK health insurance fund in southern Germany to improve ambulatory care for patients with musculoskeletal disorders. The program offers extended consultation times, structured collaboration between general practitioners and specialists, as well as a renewed focus on guideline-recommended therapies and patient empowerment. The aim of this study was to assess the impact of the program on health service utilization in patients with hip and knee osteoarthritis (OA).

Methods

This retrospective cohort study, which is based on claims data, evaluated health service utilization in patients with hip and knee OA from 2014 to 2017. The intervention group comprised OA patients enrolled in collaborative ambulatory orthopedic care, and the control group received usual care. The outcomes were participation in exercise interventions, prescription of physical therapy, OA-related hospitalization, and endoprosthetic surgery rates. Generalized linear regression models were used to analyze the effect of the intervention.

Results

Claims data for 24,170 patients were analyzed. Data for the 23,042 patients in the intervention group were compared with data for the 1,128 patients in the control group. Participation in exercise interventions (Odds Ratio (OR): 1.781; 95% Confidence Interval (CI): 1.230–2.577; p = 0.0022), and overall prescriptions of physical therapy (Rate Ratio (RR): 1.126; 95% CI: 1.025–1.236; p = 0.0128) were significantly higher in the intervention group. The intervention group had a significantly lower risk of OA -related hospitalization (OR: 0.375; 95% CI: 0.290–0.485; p < 0.0001). Endoprosthetic surgery of the knee was performed in 53.8% of hospitalized patients in the intervention group vs. 57.5% in the control group; 27.7% of hospitalized patients underwent endoprosthetic surgery of the hip in the intervention group versus 37.0% in the control group.

Conclusions

In patients with hip and knee OA, collaborative ambulatory orthopedic care is associated with a lower risk of OA-related hospitalization, higher participation in exercise interventions, and more frequently prescribed physical therapy.
Cementless femoral neck endoprosthesis SPIRON in men in aspects of clinical status and quality of life in an average 7-year follow-up
Authors: Stołtny Tomasz , Dugiełło Bogdan , Pyda Michał , Pasek Jarosław , Rokicka Dominika , Wróbel Marta , Augustyn Aleksander , Spyrka Daniel , Białek Michał , Strojek Krzysztof , Koczy Bogdan
Published: August 2022

Background

We report the clinical evaluation, quality of life and pain assessment in patients who had a femoral neck SPIRON endoprosthesis.

Methods

The study group consisted of 27 men in whom 35 femoral neck endoprosthesis were implanted (8 on the left side, 12 on the right side and 7 bilateral) due to idiopathic osteoarthritis of the hip (20 patients) or avascular femoral osteonecrosis (7 patients) in a mean 7-year follow-up.

Results

The median pre-operative Harris Hip score (HHS) was 35.5 and post-operative 98.5 (p < 0.001). The median WOMAC HIP score was pre-operatively 57 and post-operatively 0 (p < 0.001). The median SF-12 score was pre-operatively 4 and post-operatively 33 (p < 0.001). The median pain assessment in VAS scale was 7 pre-operatively and 0 post-operatively (p < 0.001).

Conclusions

The results of all examined patients have changed significantly in every category showing that SPIRON endoprosthesis improved their quality of life and statistically reduced pain ailments. Moreover we have proved that higher BMI (> 30) is associated with worse operation outcomes.
Exploration of fertility and early menopause related information needs and development of online information for young breast cancer survivors
Authors: Sparidaens Ellen Marie , Beerendonk Catharina C. M. , Fleischer Kathrin , Nelen Willianne L. D. M. , Braat Didi D. M. , Hermens Rosella P. M. G.
Published: August 2022

Background

Approximately half of premenopausal women diagnosed with breast cancer desire to conceive after they finish treatment. Counseling about the risk of infertility prior to cancer treatment has been proven to improve quality of life after cancer treatment. As a result of this, guidelines focus on informing women on this topic prior to treatment. However, it is equally important to provide fertility related information after primary treatment has been completed, when the wish to conceive might become actual. Therefore, the aim of this study was to identify the fertility and early menopause related information needs of young breast cancer survivors and to design, develop and implement online information material with input of stakeholders.

Methods

A phenomenological qualitative study consisting of four phases was performed: identification of information needs through semi-structured interviews from a professional perspective (1) and a patient perspective (2). Exploration of stakeholders perspective regarding development and implementation of online information material (3) and development and implementation of the information material (4).

Results

Professionals indicated that there are no guidelines regarding the provision of fertility related information during cancer survivorship. Survivors reported unmet information needs. Women identified the following as most important information needs (a) fertility preservation options, (b) the risk of menopause or infertility, and (c) long term consequences of early menopause. A wide range of stakeholders involved in breast cancer care were interviewed. Based on their proposed design the information material was implemented on a nationwide website aiming at informing and supporting breast cancer patients.

Conclusions

Fertility and early menopause related information needs of young breast cancer survivors and their professionals were identified. Information material has been designed, developed and nationally implemented. This way, professionals in breast cancer care are provided with an information tool that helps them meet the information needs and preferences of their patients.
A survey of implicit bias training in physician assistant and nurse practitioner postgraduate fellowship/residency programs
Authors: Kidd Vasco Deon , Spisak Jennifer M. , Vanderlinden Sarah , Kayingo Gerald
Published: August 2022

Background

There has been renewed focus on advancing inclusivity within organized medicine to reduce health disparities and achieve health equity by addressing the deleterious effects of implicit bias in healthcare and clinical outcomes. It is well documented that negative implicit attitudes and stereotypes perpetuate inequity in healthcare.

The aim of this study is to investigate implicit bias training in postgraduate physician assistant (PA) and nurse practitioner (NP) education; describe delivery of content to trainees; and detail program directors’ attitudes toward this type of training. Although there is research examining implicit bias training in physician residency education, there are no published studies on implicit bias training in postgraduate PA and NP postgraduate residency/fellowship programs.

Method

A non-experimental, descriptive study was designed to obtain information via survey from members of the Association of Postgraduate Physician Assistant Programs (APPAP).

Results

The response rate was 41%. The majority of respondents (76%) felt that PA and NP postgraduate programs should include implicit bias instruction. Educational strategies used by PA and joint PA/NP postgraduate programs or their sponsoring institution to deliver implicit bias content to trainees include: implicit bias training modules (50%), facilitated group discussions (36%), invited speaker on implicit bias (33%), case studies on implicit bias (16%), and implicit association test (10%); however, 30% of postgraduate programs do not provide implicit bias training to PA and/or NP trainees. Barriers to implementing implicit bias training expressed by some postgraduate programs include: uncertainty in how to incorporate implicit bias training (16%); lack of strategic alignment with training program or sponsoring institution (13%); time constraints (10%); financial constraints (6%); lack of access to content experts (6%); and unfamiliarity with evidence supporting implicit bias training (6%).

Conclusion

The present study sheds some light on the current state of implicit bias training in PA and joint PA/NP postgraduate residency/fellowship programs. While the majority of programs offer some sort of implicit bias training, there is a need to standardize this training in PA and joint PA/NP postgraduate education curricula using an actionable framework.
Evolutionary conserved relocation of chromatin remodeling complexes to the mitotic apparatus
Authors: Messina Giovanni , Prozzillo Yuri , Monache Francesca Delle , Santopietro Maria Virginia , Dimitri Patrizio
Published: August 2022

Background

ATP-dependent chromatin remodeling complexes are multi-protein machines highly conserved across eukaryotic genomes. They control sliding and displacing of the nucleosomes, modulating histone-DNA interactions and making nucleosomal DNA more accessible to specific binding proteins during replication, transcription, and DNA repair, which are processes involved in cell division. The SRCAP and p400/Tip60 chromatin remodeling complexes in humans and the related Drosophila Tip60 complex belong to the evolutionary conserved INO80 family, whose main function is promoting the exchange of canonical histone H2A with the histone variant H2A in different eukaryotic species. Some subunits of these complexes were additionally shown to relocate to the mitotic apparatus and proposed to play direct roles in cell division in human cells. However, whether this phenomenon reflects a more general function of remodeling complex components and its evolutionary conservation remains unexplored.

Results

We have combined cell biology, reverse genetics, and biochemical approaches to study the subcellular distribution of a number of subunits belonging to the SRCAP and p400/Tip60 complexes and assess their involvement during cell division progression in HeLa cells. Interestingly, beyond their canonical chromatin localization, the subunits under investigation accumulate at different sites of the mitotic apparatus (centrosomes, spindle, and midbody), with their depletion yielding an array of aberrant outcomes of mitosis and cytokinesis, thus causing genomic instability. Importantly, this behavior was conserved by the Drosophila melanogaster orthologs tested, despite the evolutionary divergence between fly and humans has been estimated at approximately 780 million years ago.

Conclusions

Overall, our results support the existence of evolutionarily conserved diverse roles of chromatin remodeling complexes, whereby subunits of the SRCAP and p400/Tip60 complexes relocate from the interphase chromatin to the mitotic apparatus, playing moonlighting functions required for proper execution of cell division.
Effect of radiant catalytic ionization on environmental conditions in rodent rooms and the haematological status of mice
Authors: Niemiec Tomasz , Skowron Krzysztof , Świderek Wiesław , Kwiecińska-Piróg Joanna , Gryń Grzegorz , Wójcik-Trechcińska Urszula , Gajewska Marta , Zglińska Klara , Łozicki Andrzej , Koczoń Piotr
Published: August 2022

High stocking densities, closed animal houses, and elevated concentrations of bacteria, fungi, and the products of their activity, including ammonia and hydrogen sulphide, have adverse health effects. Active techniques used to reduce unfavourable environmental conditions, such as ventilation, sprinkling, bedding sorbents, and nutritional treatments, are not always sufficient to improve the animals’ living environment. The current paper aims to evaluate the effect of radiant catalytic ionization (RCI) on airborne microorganisms, cage microbiological status, gaseous ammonia concentrations, and the haematological status of mice in animal houses. After one week of operation of an RCI system, the number of airborne bacteria and fungi in the experimental room decreased in comparison to the first day of the experiment (p < 0.05 and p < 0.05 respectively), as did the concentrations of ammonia (p < 0.01) and dust. At the same time, the basic health parameters of the mice, determined in the blood, were very similar between the control and experimental room. RCI seems to be an ideal solution to ensure high hygiene standards in animal rooms and houses with limited use of disinfectants or antibiotic treatment of sick animals. An additional, environmental benefit is the limited amount of nitrogen released.
Decreased humoral immune response in the bronchi of rapid decliners with chronic obstructive pulmonary disease
Authors: Di Stefano Antonino , Dossena Francesca , Gnemmi Isabella , D’Anna Silvestro Ennio , Brun Paola , Balbi Bruno , Piraino Alessio , Spanevello Antonio , Nucera Francesco , Carriero Vitina , Bertolini Francesca , Maniscalco Mauro , Adcock Ian M. , Caramori Gaetano , Ricciardolo Fabio L. M.
Published: August 2022

Background

Identification of COPD patients with a rapid decline in FEV1 is of particular interest for prognostic and therapeutic reasons.

Objective

To determine the expression of markers of inflammation in COPD patients with rapid functional decline in comparison to slow or no decliners.

Methods

In COPD patients monitored for at least 3 years (mean ± SD: 5.8 ± 3 years) for lung functional decline, the expression and localization of inflammatory markers was measured in bronchial biopsies of patients with no lung functional decline (FEV1% + 30 ± 43 ml/year, n = 21), slow (FEV1% ml/year, − 40 ± 19, n = 14) and rapid decline (FEV1% ml/year, − 112 ± 53, n = 15) using immunohistochemistry. ELISA test was used for polymeric immunoglobulin receptor (pIgR) quantitation “in vitro”.

Results

The expression of secretory IgA was significantly reduced in bronchial epithelium (p = 0.011) and plasma cell numbers was significantly reduced in the bronchial lamina propria (p = 0.017) of rapid decliners compared to no decliners. Bronchial inflammatory cell infiltration, CD4, CD8, CD68, CD20, NK, neutrophils, eosinophils, mast cells, pIgR, was not changed in epithelium and lamina propria of rapid decliners compared to other groups. Plasma cells/mm2 correlated positively with scored total IgA in lamina propria of all patients. “In vitro” stimulation of 16HBE cells with LPS (10 μg/ml) and IL-8 (10 ng/ml) induced a significant increase while H2O2 (100 μM) significantly decreased pIgR epithelial expression.

Conclusion

These data show an impaired humoral immune response in rapid decliners with COPD, marked by reduced epithelial secretory IgA and plasma cell numbers in the bronchial lamina propria. These findings may help in the prognostic stratification and treatment of COPD.
Non-invasive brain stimulation for improving gait, balance, and lower limbs motor function in stroke
Authors: Veldema Jitka , Gharabaghi Alireza
Published: August 2022

Objectives

This systematic review and meta-analysis aim to summarize and analyze the available evidence of non-invasive brain stimulation/spinal cord stimulation on gait, balance and/or lower limb motor recovery in stroke patients.

Methods

The PubMed database was searched from its inception through to 31/03/2021 for randomized controlled trials investigating repetitive transcranial magnetic stimulation or transcranial/trans-spinal direct current/alternating current stimulation for improving gait, balance and/or lower limb motor function in stroke patients.

Results

Overall, 25 appropriate studies (including 657 stroke subjects) were found. The data indicates that non-invasive brain stimulation/spinal cord stimulation is effective in supporting recovery. However, the effects are inhomogeneous across studies: (1) transcranial/trans-spinal direct current/alternating current stimulation induce greater effects than repetitive transcranial magnetic stimulation, and (2) bilateral application of non-invasive brain stimulation is superior to unilateral stimulation.

Conclusions

The current evidence encourages further research and suggests that more individualized approaches are necessary for increasing effect sizes in stroke patients.
Salvianolic acid B activates chondrocytes autophagy and reduces chondrocyte apoptosis in obese mice via the KCNQ1OT1/miR-128-3p/SIRT1 signaling pathways
Authors: Sun Tianwen , Wang Fei , Hu Gaojian , Li Zhizhou
Published: August 2022

Purpose

Salvianolic acid B (Sal B) possesses strong anti-inflammatory and antioxidant activity. This study aims to explore the underlying mechanism of Sal B to improve the obesity-related osteoarthritis (OA).

Methods

C57BL/6 J male mice were fed with a normal control diet (NCD), a high fat diet (HFD), or HFD with Sal B (25 mg/kg), and mouse body weights and osteoarticular inflammatory factor levels were examined. Mouse chondrogenic cell line ATDC5 were transfected with lncRNA KCNQ1 overlapping transcript 1 small hairpin RNA (KCNQ1OT1 shRNA), miR-128-3p mimic or Sirtuin-1 small interfering RNA (SIRT1 siRNA), then stimulated with Palmitic acid (PA) followed by the treatment of Sal B. Then, inflammatory response, apoptosis, and autophagy of ATDC5 cells in different groups were detected.

Results

Sal B reduced the body weight, decreased the levels of inflammatory markers, and improved cartilage damage in OA mice fed with HFD. KCNQ1OT1 was downregulated in OA mice fed with HFD, and PA-stimulated ATDC5 cells. Sal B protected ATDC5 cells against PA-mediated inflammation, apoptosis, and the inhibition of autophagy, while knockdown of KCNQ1OT1 reversed these results. KCNQ1OT1 was found to be functioned as a ceRNA to bind and downregulate the expression of miR-128-3p that was upregulated in PA-induced cells. Furthermore, SIRT1 was verified as a target of miR-128-3p. MiR-128-3p overexpression reversed the effects of Sal B on inflammatory response, apoptosis, and autophagy in PA-stimulated cells, and knockdown of SIRT1 displayed the similar results.

Conclusion

Sal B exerted a chondroprotective effect by upregulating KCNQ1OT1, which indicates Sal B can used for a therapeutic agent in obesity-related OA.
Macrophage-mediated tissue response evoked by subchronic inhalation of lead oxide nanoparticles is associated with the alteration of phospholipases C and cholesterol transporters
Authors: Smutná Tereza , Dumková Jana , Kristeková Daniela , Laštovičková Markéta , Jedličková Adriena , Vrlíková Lucie , Dočekal Bohumil , Alexa Lukáš , Kotasová Hana , Pelková Vendula , Večeřa Zbyněk , Křůmal Kamil , Petráš Jiří , Coufalík Pavel , Všianský Dalibor , Záchej Samuel , Pinkas Dominik , Vondráček Jan , Hampl Aleš , Mikuška Pavel , Buchtová Marcela
Published: August 2022

Background

Inhalation of lead oxide nanoparticles (PbO NPs), which are emitted to the environment by high-temperature technological processes, heavily impairs target organs. These nanoparticles pass through the lung barrier and are distributed via the blood into secondary target organs, where they cause numerous pathological alterations. Here, we studied in detail, macrophages as specialized cells involved in the innate and adaptive immune response in selected target organs to unravel their potential involvement in reaction to subchronic PbO NP inhalation. In this context, we also tackled possible alterations in lipid uptake in the lungs and liver, which is usually associated with foam macrophage formation.

Results

The histopathological analysis of PbO NP exposed lung revealed serious chronic inflammation of lung tissues. The number of total and foam macrophages was significantly increased in lung, and they contained numerous cholesterol crystals. PbO NP inhalation induced changes in expression of phospholipases C (PLC) as enzymes linked to macrophage-mediated inflammation in lungs. In the liver, the subchronic inhalation of PbO NPs caused predominantly hyperemia, microsteatosis or remodeling of the liver parenchyma, and the number of liver macrophages also significantly was increased. The gene and protein expression of a cholesterol transporter CD36, which is associated with lipid metabolism, was altered in the liver. The amount of selected cholesteryl esters (CE 16:0, CE 18:1, CE 20:4, CE 22:6) in liver tissue was decreased after subchronic PbO NP inhalation, while total and free cholesterol in liver tissue was slightly increased. Gene and protein expression of phospholipase PLCβ1 and receptor CD36 in human hepatocytes were affected also in in vitro experiments after acute PbO NP exposure. No microscopic or serious functional kidney alterations were detected after subchronic PbO NP exposure and CD68 positive cells were present in the physiological mode in its interstitial tissues.

Conclusion

Our study revealed the association of increased cholesterol and lipid storage in targeted tissues with the alteration of scavenger receptors and phospholipases C after subchronic inhalation of PbO NPs and yet uncovered processes, which can contribute to steatosis in liver after metal nanoparticles exposure.

Graphical abstract
Oral eltanexor treatment of patients with higher-risk myelodysplastic syndrome refractory to hypomethylating agents
Authors: Lee Sangmin , Mohan Sanjay , Knupp Jessica , Chamoun Kamal , de Jonge Adrienne , Yang Fan , Baloglu Erkan , Shah Jatin , Kauffman Michael G. , Shacham Sharon , Bhatnagar Bhavana
Published: August 2022

Patients with higher-risk myelodysplastic syndromes (MDS) refractory to hypomethylating agents (HMAs) have limited therapeutic options and an expected overall survival (OS) of 3–5 months. Eltanexor is an investigational oral selective inhibitor of nuclear export with low central nervous system penetrance and an acceptable tolerability profile. Preclinical studies suggest that myeloid malignancies are sensitive to nuclear export inhibition. Eltanexor exhibited efficacy in hematologic models, supporting exploration in a clinical trial. This phase 1/2 study (NCT02649790) assessed single-agent activity of eltanexor in patients with higher-risk MDS and 5–19% myeloblasts. Two starting doses of eltanexor were evaluated: 20 mg (n = 15), 10 mg (n = 5), both administered on days 1–5 each week of a 28-day cycle. Twenty patients with primary HMA-refractory MDS, with a median age of 77 years (range 62–89), and a median of two prior treatment regimens (range 1–4) were enrolled. Of these, 15 were evaluated for efficacy and 20 for safety. The overall response rate (ORR) was 53.3%, with seven patients (46.7%) achieving marrow complete remission (mCR) and one additional patient achieving hematologic improvement (HI). In the 10 mg group, three patients (60%) reached mCR and two (40%) stable disease (SD), while for 20 mg, four patients (40%) had mCR and two (20%) SD. A total of three patients (20%) had HI and became transfusion independent ≥ 8 weeks. Median OS for the efficacy-evaluable patients (n = 15) was 9.86 months (7.98, NE). Overall, the most frequently reported treatment-related adverse events were nausea (45%), diarrhea (35%), decreased appetite (35%), fatigue and neutropenia (both 30%). Single-agent oral eltanexor was active, safe, and well tolerated in patients with higher-risk, primary HMA-refractory MDS.
Muscular myostatin gene expression and plasma concentrations are decreased in critically ill patients
Authors: Grunow Julius J. , Reiher Katja , Carbon Niklas M. , Engelhardt Lilian Jo , Mai Knut , Koch Susanne , Schefold Joerg C. , Z’Graggen Werner , Schaller Stefan J. , Fielitz Jens , Spranger Joachim , Weber-Carstens Steffen , Wollersheim Tobias
Published: August 2022

Background

The objective was to investigate the role of gene expression and plasma levels of the muscular protein myostatin in intensive care unit-acquired weakness (ICUAW). This was performed to evaluate a potential clinical and/or pathophysiological rationale of therapeutic myostatin inhibition.

Methods

A retrospective analysis from pooled data of two prospective studies to assess the dynamics of myostatin plasma concentrations (day 4, 8 and 14) and myostatin gene (MSTN) expression levels in skeletal muscle (day 15) was performed. Associations of myostatin to clinical and electrophysiological outcomes, muscular metabolism and muscular atrophy pathways were investigated.

Results

MSTN gene expression (median [IQR] fold change: 1.00 [0.68–1.54] vs. 0.26 [0.11–0.80]; p = 0.004) and myostatin plasma concentrations were significantly reduced in all critically ill patients when compared to healthy controls. In critically ill patients, myostatin plasma concentrations increased over time (median [IQR] fold change: day 4: 0.13 [0.08/0.21] vs. day 8: 0.23 [0.10/0.43] vs. day 14: 0.40 [0.26/0.61]; p < 0.001). Patients with ICUAW versus without ICUAW showed significantly lower MSTN gene expression levels (median [IQR] fold change: 0.17 [0.10/0.33] and 0.51 [0.20/0.86]; p = 0.047). Myostatin levels were directly correlated with muscle strength (correlation coefficient 0.339; p = 0.020) and insulin sensitivity index (correlation coefficient 0.357; p = 0.015). No association was observed between myostatin plasma concentrations as well as MSTN expression levels and levels of mobilization, electrophysiological variables, or markers of atrophy pathways.

Conclusion

Muscular gene expression and systemic protein levels of myostatin are downregulated during critical illness. The previously proposed therapeutic inhibition of myostatin does therefore not seem to have a pathophysiological rationale to improve muscle quality in critically ill patients.

Trial registration: ISRCTN77569430—13th of February 2008 and ISRCTN19392591 17th of February 2011.

Graphical abstract
Topical administration of the secretome derived from human amniotic epithelial cells ameliorates psoriasis-like skin lesions in mice
Authors: Yang Mengbo , Wang Lanqi , Chen Zhimin , Hao Weijie , You Qian , Lin Jianhua , Tang Jingzhi , Zhao Xin , Gao Wei-Qiang , Xu Huiming
Published: August 2022

Background

Psoriasis is a chronic inflammatory skin disease. Tissue stem cells have exhibited a therapeutic effect on psoriatic mice. However, the therapeutic effect of topical administration of the secretome derived from tissue stem cells on psoriasis has not been reported.

Methods

The secretome from human amniotic epithelial cells (AEC-SC) and human umbilical cord mesenchymal stem cells (UMSC-SC) was topically administrated on the back of imiquimod-induced psoriasis-like mice. Subsequently, we observed the skin lesions and skin inflammation of psoriasis-like mice. Next, we further analyzed the paracrine factors in AEC-SC and UMSC-SC by protein chips. Lastly, the effect of the crucial paracrine factor was investigated by imiquimod-induced psoriasis-like mice.

Results

We found that AEC-SC had a better therapeutic effect on attenuating psoriasis-like skin lesions including skin scales, skin redness and skin thickness than UMSC-SC, and it had a better regulatory effect on keratinocyte hyperproliferation and altered differentiation. Thus, we focused on AEC-SC. Further study showed that AEC-SC reduced the infiltration of neutrophils and interleukin-17-producing T cells. Next, the analysis of AEC-SC with protein chip revealed that the levels of anti-inflammatory factor interleukin-1 receptor antagonist (IL-1ra) were much higher in AEC-SC compared to that in UMSC-SC. More importantly, the beneficial effect of AEC-SC on psoriasis-like skin lesions and skin inflammation of mice were significantly impaired when neutralizing with IL-1ra antibody, while the recombinant human IL-1ra showed a less protective effect than AEC-SC.

Conclusions

The present study demonstrated that AEC-SC could efficiently ameliorate psoriasis-like skin lesions and skin inflammation and IL-1ra plays an essential role. Therefore, topical administration of AEC-SC may provide a novel strategy for treating psoriasis-like inflammatory skin diseases.
Irisin enhances chondrogenic differentiation of human mesenchymal stem cells via Rap1/PI3K/AKT axis
Authors: Chen Taiqiu , Peng Yan , Hu Wenjun , Shi Huihong , Li Pengfei , Que Yichen , Qiu Jincheng , Qiu Xianjian , Gao Bo , Zhou Hang , Chen Yanbo , Zhu Yuanxin , Li Shaoguang , Liang Anjing , Gao Wenjie , Huang Dongsheng
Published: August 2022

Background

Human mesenchymal stem cells (hMSCs) have been proven to have inherent chondrogenic differentiation potential, which appears to be used in cartilage regeneration. Increasing evidence suggests that irisin enhances osteoblast differentiation of MSCs, but little is known about its potential on chondrogenic differentiation.

Methods

In the study, we investigated the effects of irisin on chondrogenic differentiation of hMSCs using a high-density pellet culture system. The cartilage pellets were evaluated by morphology, and the metabolism of cartilage matrix was detected by qPCR, western blot and immunohistochemistry. Next, RNA-seq was performed to explore the underlying mechanism. Furthermore, using the transduction of plasmid, miRNAs mimics and inhibitor, the activation of Rap1/PI3K/AKT axis, the expression level of SIPA1L2, and the functional verification of miR-125b-5p were detected on day 7 of chondrogenic differentiation of hMSCs.

Results

Compared with the controls, we found that irisin treatment could significantly enhance the chondrogenic differentiation of hMSCs, enlarge the induced-cartilage tissue and up-regulate the expression levels of cartilage markers. RNA-seq indicated that irisin activated the Rap1 and PI3K/AKT signaling pathway, and the lower expression level of SIPA1L2 and the higher expression level of miR-125b-5p were found in irisin-treated group. Further, we found that irisin treatment could up-regulate the expression level of miR-125b-5p, targeting SIPA1L2 and consequently activating the Rap1/PI3K/AKT axis on the process of chondrogenic differentiation of hMSCs.

Conclusions

Collectively, our study reveals that irisin can enhance chondrogenic differentiation of hMSCs via the Rap1/PI3K/AKT pathway, suggesting that irisin possesses prospects in cartilage regeneration.
Transmission and innovation on gold granulation: the application of tin for soldering techniques in ancient China
Authors: Shi Yong , Wen Yadi , Li Xiaojun , Liu Zhaojian , Huang Yumin , He Bei
Published: August 2022

Granulation, an ancient metal processing technique mainly applied to gold, has originated from West Asia, and later appeared at many different archaeological sites across the Eurasia. The distribution of granulated gold ornaments bearing diverse soldering techniques reveal the long-distance human interaction across the Eurasia. This paper presents the scientific analysis of the surface morphology and elemental composition of two granulated gold ornaments from Tushan Tomb No.2 pit in Xuzhou, Jiangsu Province, which approximately dated to the first century CE of Han Dynasty. Multiple non-destructive analytical methods including Ultra-Depth Three-Dimensional Microscope, Energy dispersive X-ray fluorescence spectrometer (XRF) and Scanning electron microscope with energy dispersive X-Ray spectrometer (SEM-EDS) were conducted to obtain analytical data. The result indicates that tin-participated soldering technique has been adopted to accomplish the granulation. Although the usage of tin has been mentioned in a former study as “a secret of Etruscan granulation”, the lack of quantitative analyses leaves this assumption unconvinced. Our findings on Tushan ornaments throw light on this issue by illustrating the regular distribution pattern of the tin content at the joints, which appears to be intentionally added for certain amount. Although tiny in size, the gold granules record the secret of soldering techniques used in China and many other regions across the Eurasia during the ancient time, complementing the study of granulation techniques and reflecting the transmission and innovation along with the technological and cultural contacts.
Supporting self-recovery in post-conflict situations: a case study of Syria
Authors: Raeburn-Gibson Taylor
Published: August 2022

Supporting shelter self-recovery is a modality of humanitarian aid which remains ill-defined and misunderstood despite the many aid organizations that utilize this approach. Of the little existing knowledge and best practices regarding self-recovery support methods, most has been developed for natural disaster contexts, and not post-conflict. Post-conflict situations are much more complex than disasters due to a multitude of economic, social, and other factors. Further research is greatly needed to support self-recovery programs in post-conflict situations, especially due to the complexities involved. This research aims to highlight the unique complexities of post-conflict support to self-recovery and to identify ways of improving this support. This is done through a combination of a literature review and a case study of self-recovery support methods currently being employed in Syria. The results include a framework which identifies and categorizes common factors, barriers, and facilitators which influence the implementation of self-recovery support projects. The results also include a list of recommendations to improve these projects for stakeholders involved. Based on an analysis of these recommendations, five Key Areas for Action are discussed which are as follows: maximizing implementing organizations’ capacities, contextualizing risks, increasing adaptable and flexible programming, addressing the social dimension, and improving international coordination.