bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the physiologic paradoxes that underlie exercise prescription for stress fracture prevention
Authors: Guerriere Katelyn I , Castellani Colleen M , Popp Kristin L , Bouxsein Mary L , Hughes Julie M
Published: August 2022

The effects of exercise on stress fracture risk are paradoxical. Exercise can promote both bone formation and resorption, which in turn, can reduce and increase risk of stress fractures, respectively. We review classic and current literature that suggests that the processes that underlie these responses to exercise are distinct. Bone remodeling involves osteoclastic resorption of fatigue-damaged bone, coupled with subsequent bone deposition to replace the damaged tissue. Bone modeling involves the independent action of osteoblasts and osteoclasts forming or resorbing bone, respectively, on a surface. In the formation mode, modeling results in increased bone stiffness, strength, and resistance to fatigue. Both the remodeling and modeling responses to exercise require significant time for newly deposited bone to fully mineralize. We propose that recognizing these two distinct physiologic pathways and their related time courses reveals the theoretical basis to guide exercise prescription to promote bone health during periods of heightened stress fracture risk. Such guidance may include minimizing rapid increases in the duration of repetitive exercises that may cause fatigue damage accrual, such as long-distance running and marching. Rather, limiting initial exercise characteristics to those known to stimulate bone formation, such as short-duration, moderate-to-high impact, dynamic, and multidirectional activities with rest insertion, may increase the fatigue resistance of bone and consequently minimize stress fracture risk.
The skeleton in a physical world
Authors: Rubin Janet , Styner Maya
Published: August 2022

All organisms exist within a physical space and respond to physical forces as part of daily life. In higher organisms, the skeleton is critical for locomotion in the physical environment, providing a carapace upon which the animal can move to accomplish functions necessary for living. As such, the skeleton has responded evolutionarily, and does in real-time, to physical stresses placed on it to ensure that its structure supports its function in the sea, in the air, and on dry land. In this article, we consider how those cells responsible for remodeling skeletal structure respond to mechanical force including load magnitude, frequency, and cyclicity, and how force rearranges cellular structure in turn. The effects of these forces to balance the mesenchymal stem cell supply of bone-forming osteoblasts and energy storing adipocytes are addressed. That this phenotypic switching is achieved at the level of both gene transactivation and alteration of structural epigenetic controls of gene expression is considered. Finally, as clinicians, we consider this information as it applies to a prescriptive for intelligent exercise.
Vitamin D levels and human sperm DNA fragmentation: a prospective, cohort study
Authors: Blaseg Elise , Von Wald Tiffany , Hansen Keith A.
Published: August 2022

Background

Intracytoplasmic sperm injection (ICSI) has revolutionized the treatment of couples with male factor infertility but results remain suboptimal and suggest the need for further investigation into the molecular biology of spermatozoa. Vitamin D has been implicated in spermatogenesis and sperm function. Hypovitaminosis D has been associated with abnormal testicular function, including elevated sperm DNA fragmentation in a murine model. This study’s objective was to evaluate if there is a correlation between Vitamin D sufficiency and human spermatozoa DNA fragmentation index % (DFI%) in infertile couples.

Results

A prospective cohort study using a consecutive, convenience sample of subjects with infertility. The primary endpoint was the effect of Vitamin D sufficiency on human spermatozoa DFI%, and secondary outcomes included Vitamin D’s effect on moderate DFI%, high DFI%, High DNA stainability % (HDS%), sperm density (million/mL), sperm total motility (% total) and sperm strict morphology (% total). Of the 111 participating, 9 were excluded, leaving 102subjects. The subjects were stratified by vitamin D levels: deficient (< 20 ng/mL; n = 24), insufficient (20–30 ng/mL; n = 43),, and sufficient (> 30 ng/mL; n = 35). There were no statistical difference between the categories of serum vitamin D levels and sperm DFI% as well as the secondary outcomes. An increased BMI was associated with low serum vitamin D levels (p = 0.0012).

Conclusion

Vitamin D deficiency was not associated with sperm DFI% or routine sperm parameters. Previous animal and human studies have demonstrated conflicting results between sperm parameters and Vitamin D levels. Redundant pathways in Vitamin D and calcium homeostasis in the human male reproductive tract may maintain essential reproductive processes during Vitamin D insufficiency or deficiency.

Trial registration

Trial Registration Number: MOD00002311 (ClinicalTrials.gov).
Comprehensive analysis of differentially expressed profiles of mRNA, lncRNA, and miRNA of Yili geese ovary at different egg-laying stages
Authors: Zhao Xiaoyu , Wu Yingping , Li Haiying , Li Jiahui , Yao Yingying , Cao Yan , Mei Zhiyong
Published: August 2022

Background

The development of the ovaries is an important factor that affects egg production performance in geese. Ovarian development is regulated by genes that are expressed dynamically and stage-specifically. The transcriptome profile analysis on ovarian tissues of goose at different egg laying stages could provide an important basis for screening and identifying key genes regulating ovarian development.

Results

In this study, 4 ovary tissues at each breeding period of pre-laying (PP), laying (LP), and ceased-laying period (CP), respectively, with significant morphology difference, were used for RNA extraction and mRNAs, lncRNAs, and miRNAs comparison in Yili geese. CeRNA regulatory network was constructed for key genes screening. A total of 337, 1136, and 525 differentially expressed DE mRNAs, 466, 925, and 742 DE lncRNAs and 258, 1131 and 909 DE miRNAs were identified between PP and LP, between CP and LP, and between CP and PP groups, respectively. Functional enrichment analysis showed that the differentially expressed mRNAs and non-coding RNA target genes were mainly involved in the cell process, cytokine-cytokine receptor interaction, phagosome, calcium signaling pathway, steroid biosynthesis and ECM-receptor interaction. Differential genes and non-coding RNAs, PDGFRB, ERBB4, LHCGR, MSTRG.129094.34, MSTRG.3524.1 and gga-miR-145–5p, related to reproduction and ovarian development were highly enriched. Furthermore, lncRNA-miRNA-mRNA regulatory networks related to ovary development were constructed.

Conclusions

Our study found dramatic transcriptomic differences in ovaries of Yili geese at different egg-laying stages, and a differential lncRNA-miRNA-mRNA regulatory network related to cell proliferation, differentiation and apoptosis and involved in stromal follicle development were established and preliminarily validated, which could be regarded as a key regulatory pathway of ovarian development in Yili geese.
Effect of individualized treatment strategy on postoperative nausea and vomiting in gynaecological laparoscopic surgery: a double-blind, randomized, controlled trial
Authors: Ma Wenjing , Qi Yupeng , Liu Can , Wang Mingfang , Zhang Yun , Yao Weidong
Published: August 2022

Background

Postoperative nausea and vomiting (PONV) have always been a concern of clinicians and may increase medical costs for patients. Consensus guidelines recommend using multiple antiemetics with different mechanisms as prophylaxis in patients at high risk of PONV. Individualized risk scores for nausea and vomiting and individualized treatment strategies are feasible. This study evaluated the effect of individualized treatment strategies on postoperative nausea and vomiting after laparoscopic gynaecological operations.

Methods

This was a double-blind, randomized, controlled trial. A total of 119 adult patients who underwent gynaecological laparoscopic surgery under general anaesthesia were randomly divided into an individualized treatment group or a control group, with the individualized treatment group receiving individualized prevention according to a preoperative risk score of nausea and vomiting and the control group receiving no individualized prevention. Vomiting, retching, nausea, and use of rescue medication were all recorded for 24 h after the operation. The primary outcome variable was complete response, defined as no emesis or the use of rescue medication 24 h postoperatively.

Results

The complete response rate was higher in the individualized treatment group (56.7%) than in the control group (23.7%) (95% CI, 0.01–0.27; P < 0.001). The incidences of emesis (18.3% vs. 44.1%, P = 0.002) were significantly lower in the individualized treatment group than in the control group. There were no differences in any nausea (26.7% vs. 33.9%, P = 0.391) or rescue medication use (6.7% vs. 8.5%, P = 0.743). Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently in the individualized treatment group than in the control group.

Conclusion

In conclusion, this single-centre, double-blind, randomized study suggests that an individualized PONV prophylactic treatment strategy based on the number of PONV risk factors could be a safe and effective regimen to reduce the incidence of PONV in adult patients undergoing laparoscopic gynaecological surgery.
Evaluation of a pharmacist-led intervention to improve medication adherence in patients initiating dabigatran treatment: a comparison with standard pharmacy practice in Poland
Authors: Merks Piotr , Cameron Jameason D. , Balcerzak Marcin , Religioni Urszula , Świeczkowski Damian , Konstanty Mikołaj , Hering Dagmara , Szymański Filip M. , Jaguszewski Milosz , Vaillancourt Régis
Published: August 2022

Backround

Dabigatran is a direct thrombin inhibitor used to treat cardiac arrhythmias, and rates of non-adherence to dabigatran in Polish populations are high. The current study examined how a pharmacist-led intervention of counselling with pictogram-enhanced medication instructions, and smartphone medication reminders, can improve adherence to dabigatran.

Methods

A 3-month pharmacist-led intervention was conducted in community pharmacies in Poland on 325 men and women filling a dabigatran prescription for the first time. Participating pharmacies were assigned into the Control Group (n = 172 patients) or the Intervention Group (n = 153 patients). The primary outcome of this prospective study was self-reported medication adherence assessed at 3 time points (day 7, day 21, and day 90) after initiation of dabigatran.

Results

Patients in the Intervention Group were significantly more adherent (mean days on Dabigatan/week) than the Control Group at 7 days (6.0 ± 0.9 vs 5.4 ± 1.1, p < 0.0001), 21 days (5.6 ± 1.0 vs 4.9 ± 1.3, p < 0.0001), and 90 days (5.5 ± 1.3 vs 4.4 ± 2.0, p < 0.0001), respectively. The percentage of patients in the Intervention Group who reported taking dabigatran twice/day as prescribed was significantly higher than the Control Group at 7 days (82.7% vs 71.4%, p = 0.0311), at 21 days (84.4% vs 58%, p < 0.0001), and at 90 days (78.4% vs 39.7%, p < 0.0001), respectively. The proportion of patients fully adherent (every day, twice/day) at 90 days was significantly higher in the Intervention Group than in the Control Group (26.1% vs 13.2%, p = 0.0145).

Conclusions

Our findings support the role for interventions in community pharmacies in Poland to improve medication adherence, thus providing evidence for the efficacy of a pharmacist-led pictogram and smartphone-based program to support optimal dabigatran treatment.
Internet use and physical activity of older adults during the COVID-19 pandemic: a cross-sectional study in a northern Japanese City
Authors: Sasaki Sachiko , Sato Akinori , Tanabe Yoshie , Matsuoka Shinji , Adachi Atsuhiro , Kayano Toshiya , Yamazaki Hiroshi , Matsuno Yuichi , Nakano Ann , Watanabe Toshihiro
Published: August 2022

Background

Little is known of whether Internet use is associated with physical activity among socially isolated older adults during the coronavirus disease 2019 (COVID-19) pandemic. This study investigated the association between Internet use and physical activity, and whether this association differs depending on social isolation among community-dwelling Japanese older adults.

Methods

A cross-sectional study was conducted with 1048 community-dwelling residents aged 65–90 years. Data were obtained using a self-reported questionnaire in August 2020. Physical activity was assessed using the International Physical Activity Questionnaire-Short Form. Multivariable logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between Internet use and moderate-to-vigorous physical activity (MVPA).

Results

Internet use showed a significant association with MVPA (OR = 1.42, 95% CI: 1.06–1.90) after adjusting for age, sex, self-reported socioeconomic status, and other health-related characteristics. When the results were stratified by social participation and living status, Internet use was associated with a significantly higher likelihood of MVPA among participants with no social participation (OR = 1.81, 95% CI: 1.03–3.17) and living with family (OR = 1.40, 95% CI: 1.02–1.93).

Conclusion

Internet use was associated with sufficient physical activity, and this association may differ depending on the social isolation among community-dwelling older adults in Japan.
Prevalence and determinants of home delivery among reproductive age women, Margibi County, Liberia
Authors: Maximore Leroy S. , Mohammed Abdul Gafaru , Issahaku Gyesi Razak , Sackey Samuel , Kenu Ernest
Published: August 2022

Background

The use of institutional delivery services is essential for improving maternal and child health. However, studies in Liberia reveal over 20% of women still deliver at home. We assessed the prevalence and associated factors of home delivery among women of reproductive age in Margibi County, Liberia.

Methods

We conducted a cross-sectional study among 438 women of reproductive age in Margibi County. Data were obtained using a semi-structured questionnaire. A simple random sampling approach was used to select the participants for the study. We performed binary logistic regression to identify factors influencing home delivery. Findings were summarized into tables displaying the frequencies, percentages, crude, and adjusted odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Prevalence of home delivery in the County was 90.6% (95% CI = 87.5 – 93.0). Women who were ≥ 31 years (aOR = 6.74, 95%CI = 2.86—15.90), women who had two or more children (aOR = 9.68, 95%CI = 4.07—22.99) and those who had rapid onset of labor (aOR = 6.35, 95%CI = 1.59 – 25.27) were associated with increased odds of home delivery. Good attitude of health workers (aOR = 0.01, 95%CI = 0.001 – 0.08) and the availability of transport to the nearest health facility (aOR = 0.01, 95%CI = 0.003 – 0.03) were factors associated with a decreased odds of home delivery among the study participants.

Conclusion

The high prevalence of home delivery in the county is a call for urgent interventions by the government of Liberia and various non-governmental organizations. The government may need to supply the county with ambulances and ensure in-service training of health workers on good attitudes.
Association of Helicobacter pylori infection with survival outcomes in advanced gastric cancer patients treated with immune checkpoint inhibitors
Authors: Che Hebin , Xiong Qi , Ma Jinxia , Chen Shixue , Wu Huan , Xu Hongli , Hou Baicun
Published: August 2022

Background

Accumulating evidence has revealed that the gut microbiota influences the effectiveness of immune checkpoint inhibitors (ICIs) in cancer patients. As a part of the human microbiome, Helicobacter pylori (H. pylori) was reported to be associated with reduced effectiveness of anti-PD1 immunotherapy in patients with non-small-cell lung cancer (NSCLC). Gastric cancer is more closely related to H. pylori, so we conducted a retrospective analysis to verify whether the association of H. pylori and effectiveness is applicable to advanced gastric cancer (AGC) patients.

Material and methods

AGC patients who had evidence of H. pylori and received anti-PD-1 antibodies were enrolled in the study. The differences in the disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) between the H. pylori-positive group and the negative group were compared.

Results

A total of 77 patients were included in this study; 34 patients were H. pylori positive, and the prevalence of H. pylori infection was 44.2%. Compared with the H. pylori-negative group, patients in the H. pylori-positive group had a higher risk of nonclinical response to anti-PD-1 antibody, with an OR of 2.91 (95% CI: 1.13–7.50). Patients in the H. pylori-negative group had a longer OS and PFS than those in the positive group, with an estimated median OS of 17.5 months vs. 6.2 months (HR = 2.85, 95% CI: 1.70–4.78; P = 0.021) and a median PFS of 8.4 months vs. 2.7 months (HR = 3.11, 95% CI: 1.96–5.07, P = 0.008). Multivariate analysis indicated that H. pylori infection was independently associated with PFS (HR = 1.90, 95% CI: 1.10–3.30; P = 0.022).

Conclusion

Our study unveils for the first time that H. pylori infection is associated with the outcome of immunotherapy for AGC patients. Multicenter, large sample and prospective clinical studies are needed to verify the association.
Surgical revision for pancreatojejunostomy stricture: a case series of 14 patients
Authors: Guo Feng , Huang Shimeng , Wolde Tewodross Getu , Lu Zipeng , Chen Jianmin , Wu Junli , Gao Wentao , Jiang Kuirong , Miao Yi , Wei Jishu
Published: August 2022

Background

Pancreatojejunostomy stricture (PJS) is a rare long-term complication of pancreaticojejunal anastomosis. This study aimed to investigate the role of surgery in the management of pancreatojejunostomy strictures.

Methods

The database of the Pancreas Center of Nanjing Medical University was retrospectively screened for patients who underwent a surgical revision for PJS between June 2012 and August 2019, and their clinical characteristics and management modalities were reviewed.

Results

Fourteen consecutive cases were retrieved, the median age at index operation was 41.1 years (19–71). The average time between the two operations was 70.6 months (8–270 months). Index procedures included pancreaticoduodenectomy (PD) (7/14, 50%), pylorus-preserving PD (4/14, 28.6%), Berger procedure (2/14, 14.3%), and middle pancreatectomy (1/14, 7.1%). The diameter of the main pancreatic duct was < 4 mm in all 14 cases, and nine underwent pancreaticojejunostomy (PJ) stenting during the index operation. The most frequent complaints were abdominal pain (6/14, 42.9%), recurrent acute pancreatitis (6/14, 42.9%), pancreatic fistula (1/14, 7.1%), and abdominal distention (1/14, 7.1%). The diagnosis of PJ stricture was confirmed by computed tomography or magnetic resonance imaging in all cases. All patients had a main duct diameter > 5 mm before surgical revision. All patients underwent wedge excision with interrupted one-layer suturing with absorbable sutures and without stent placement. In this series, only one patient required reoperation. Upon follow-up, 11 of 12 patients had complete resolution of the PJ stricture.

Conclusion

PJS is a long-term complication of pancreatojejunostomy. Surgical revision of the anastomosis is a safe and effective treatment modality.
Acceptance of clinical decision support system to prevent venous thromboembolism among nurses: an extension of the UTAUT model
Authors: Zha Huixian , Liu Kouying , Tang Ting , Yin Yue-Heng , Dou Bei , Jiang Ling , Yan Hongyun , Tian Xingyue , Wang Rong , Xie Weiping
Published: August 2022

Background

Venous thromboembolism has been a major public health problem and caused a heavy disease burden. Venous thromboembolism clinical decision support system was proved to have a positive influence on the prevention and management of venous thromboembolism. As the direct users, nurses' acceptance of this system is of great importance to support the successful implementation of it. However, there are few relevant studies to investigate nurses' acceptance and the associated factors are still unclear.

Objective

To investigate the determinant factors of nurses' acceptance of venous thromboembolism clinical decision support system with the modified Unified Theory of Acceptance and Use of Technology.

Methods

We designed a questionnaire based on the modified Unified Theory of Acceptance and Use of Technology and then a cross-sectional survey was conducted among nurses in a tertiary hospital in Nanjing, China. Statistically, a Structural Equation Modeling -Partial Least Squares path modeling approach was applied to examine the research model.

Results

A total of 1100 valid questionnaires were recycled. The modified model explained 74.7%, 83.0% and 86% of the variance in user satisfaction, behavioral intention and user behavior, respectively. The results showed that performance expectancy (β = 0.254, p = 0.000), social influence (β = 0.136, p = 0.047), facilitating conditions (β = 0.245, p = 0.000), self-efficacy (β = 0.121, p = 0.048) and user satisfaction (β = 0.193, p = 0.001) all had significant effects on nurses' intention. Although effort expectancy (β = 0.010, p = 0.785) did not have a direct effect on nurses' intention, it could indirectly influence nurses' intention with user satisfaction as the mediator (β = 0.296, p = 0.000). User behavior was significantly predicted by facilitating conditions (β = 0.298, p = 0.000) and user intention (β = 0.654, p = 0.001).

Conclusion

The research enhances our understanding of the determinants of nurses' acceptance of venous thromboembolism clinical decision support system. Among these factors, performance expectancy was considered as the top priority. It highlights the importance of optimizing system performance to fit the users' needs. Generally, the findings in our research provide clinical technology designers and administrators with valuable information to better meet users' requirements and promote the implementation of venous thromboembolism clinical decision support system.
The potential risk of using historic claims to set bundled payment prices: the case of physical therapy after lower extremity joint replacement
Authors: Steenhuis Sander , Hofstra Geeske , Portrait France , Amankour Fatima , Koolman Xander , van der Hijden Eric
Published: August 2022

Background

One of the most significant challenges of implementing a multi-provider bundled payment contract is to determine an appropriate, casemix-adjusted total bundle price. The most frequently used approach is to leverage historic care utilization based on claims data. However, those claims data may not accurately reflect appropriate care (e.g. due to supplier induced demand and moral hazard effects). This study aims to examine variation in claims-based costs of post-discharge primary care physical therapy (PT) utilization after total knee and hip arthroplasties (TKA/THA) for osteoarthritis patients.

Methods

This retrospective cohort study used multilevel linear regression analyses to predict the factors that explain the variation in the utilization of post-discharge PT after TKA or THA for osteoarthritis patients, based on the historic (2015–2018) claims data of a large Dutch health insurer. The factors were structured as predisposing, enabling or need factors according to the behavioral model of Andersen.

Results

The 15,309 TKA and 14,325 THA patients included in this study received an average of 20.7 (SD 11.3) and 16.7 (SD 10.1) post-discharge PT sessions, respectively. Results showed that the enabling factor ‘presence of supplementary insurance’ was the strongest predictor for post-discharge PT utilization in both groups (TKA: β = 7.46, SE = 0.498, p-value< 0.001; THA: β = 5.72, SE = 0.515, p-value< 0.001). There were also some statistically significant predisposing and need factors, but their effects were smaller.

Conclusions

This study shows that if enabling factors (such as supplementary insurance coverage or co-payments) are not taken into account in risk-adjustment of the bundle price, they may cause historic claims-based pricing methods to over- or underestimate appropriate post-discharge primary care PT use, which would result in a bundle price that is either too high or too low. Not adjusting bundle prices for all relevant casemix factors is a risk because it can hamper the successful implementation of bundled payment contracts and the desired changes in care delivery it aims to support.
A retrospective database study of the demographic features and glycemic control of patients with type 2 diabetes in Kinshasa, Democratic Republic of the Congo
Authors: Sagastume Diana , Mertens Elly , Sibongwere Deogratias Katsuva , Dimbelolo Jean-Claude , Kabundi Jean Clovis Kalobu , de Man Jeroen , Van Olmen Josefien , Peñalvo José L.
Published: August 2022

Background

The Kin-Antwerp project aimed at improving the quality of care provided to patients with diabetes in Kinshasa, the Democratic Republic of the Congo in Central Africa, including the digitalisation of routine clinical data to improve patients’ follow-up. We aim to analyse the data of a study population of Kin-Antwerp to characterise their demographic features, assess their achievement of glycemic target over time, and identify groups requiring prioritised attention.

Methods

We performed a secondary database analysis of routinely collected information from primary care patients with type 2 diabetes followed from 1991 to 2019. Data included demographics (age, sex), anthropometrics (weight, height), clinical parameters (blood pressure, plasma glucose), and anti-diabetic treatments. Achievement of glycemic target, defined as fasting plasma glucose < 126 mg/dL, over time was assessed using a multilevel mixed-effects logistic regression model.

Results

Our study population of patients with type 2 diabetes (N = 8976) comprised a higher proportion of women (67%) and patients between 40 and 65 years old (70.4%). At the first follow-up, most patients were on treatment with insulin (56.5%) and had glycemic levels under the target (79.9%). Women presented more often with obesity (27.4%) and high systolic blood pressure (41.8%) than men (8.6% and 37.0%, respectively). Patients had a median follow-up of 1.8 (interquartile range: 0.5–3.4) years. Overall, the odds of achieving glycemic target increased by 18.4% (odds ratio: 1.184, 95% CI: 1.130 to 1.239; p < 0.001) per year of follow-up. Stratified analyses suggested that the odds of achieving glycemic control over time increased among older patients (> 40 years), but not among younger patients (< 40 years).

Conclusion

In our study population, an overall poor glycemic control was observed albeit with a modest improvement in the achievement of glycemic target throughout patients’ follow-up. Younger patients may benefit from prioritised attention to achieve glycemic targets. Based on the information provided by the database, continue monitoring and improvement of the project Kin-Antwerp is recommended. Introducing further efforts to improve type 2 diabetes management should include robust glycemia-monitoring tools and haemoglobin A1c, as well as further outlining self-management strategies.
Anti-inflammation of isoliquiritigenin via the inhibition of NF-κB and MAPK in LPS-stimulated MAC-T cells
Authors: Li Manman , Lu Guicong , Ma Xiao , Wang Ruihong , Chen Xihong , Yu Yongxiong , Jiang Caode
Published: August 2022

Background

The application of plant extracts has received great interest for the treatment of bovine mastitis. Isoliquiritigenin (ISL) is a rich dietary flavonoid that has significant antioxidative, anti-inflammatory and anticancer activities. This study was conducted to explore the protective efficacy and related mechanism of ISL against lipopolysaccharide (LPS)-stimulated oxidation and inflammation in bovine mammary epithelial cells (MAC-T) by in vitro experiments.

Results

Real-time PCR and ELISA assays indicated that ISL treatment at 2.5, 5 and 10 μg/mL significantly reduced the mRNA and protein expression of the oxidative indicators cyclooxygenase-2 and inducible nitric oxide synthase (P < 0.01), and of the inflammatory cytokines interleukin-6 (P < 0.05), interleukin-1β (P < 0.01) and tumor necrosis factor-α (P < 0.01) in LPS-stimulated MAC-T cells. Moreover, Western blotting and immunofluorescence tests indicated that the phosphorylation levels of nuclear factor kappa (NF-κB) p65 and the inhibitor of NF-κB were significantly decreased by ISL treatment, thus blocking the nuclear transfer of NF-κB p65. In addition, ISL attenuated the phosphorylation levels of p38, extracellular signal-regulated kinase and c-jun NH2 terminal kinase.

Conclusions

Our data demonstrated that ISL downregulated the LPS-induced inflammatory response in MAC-T cells. The anti-inflammatory and antioxidative activity of ISL involves the NF-κB and MAPK cascades.
Enzymatic basis of the Fc-selective intra-chain disulfide reduction and free thiol content variability in an antibody produced in Escherichia coli
Authors: Baginski Tomasz K. , Veeravalli Karthik , McKenna Rebekah , Williams Christopher , Wong Katherine , Tsai Christina , Hewitt Daniel , Mani Karthik , Laird Michael W.
Published: August 2022

Background

Escherichia coli (E. coli) is a promising host for production of recombinant proteins (including antibodies and antibody fragments) that don’t require complex post-translational modifications such as glycosylation. During manufacturing-scale production of a one-armed antibody in E. coli (periplasmic production), variability in the degree of reduction of the antibody’s disulfide bonds was observed. This resulted in variability in the free thiol content, a potential critical product quality attribute. This work was initiated to understand and prevent the variability in the total free thiol content during manufacturing.

Results

In this study, we found that the reduction in antibody’s disulfide bonds was observed to occur during homogenization and the ensuing homogenate hold step where in the antibody is exposed to redox enzymes and small molecule reductants present in homogenate. Variability in the downstream processing time between the start of homogenization and end of the homogenate hold step resulted in variability in the degree of antibody disulfide bond reduction and free thiol content. The disulfide bond reduction in the homogenate is catalyzed by the enzyme disulfide bond isomerase C (DsbC) and is highly site-specific and occurred predominantly in the intra-chain disulfide bonds present in the Fc CH2 region. Our results also imply that lack of glycans in E. coli produced antibodies may facilitate DsbC accessibility to the disulfide bond in the Fc CH2 region, resulting in its reduction.

Conclusions

During E. coli antibody manufacturing processes, downstream processing steps such as homogenization and subsequent processing of the homogenate can impact degree of disulfide bond reduction in the antibody and consequently product quality attributes such as total free thiol content. Duration of the homogenate hold step should be minimized as much as possible to prevent disulfide bond reduction and free thiol formation. Other approaches such as reducing homogenate temperature, adding flocculants prior to homogenization, using enzyme inhibitors, or modulating redox environments in the homogenate should be considered to prevent antibody disulfide bond reduction during homogenization and homogenate processing steps in E. coli antibody manufacturing processes.
Ku70 affects the frequency of chromosome translocation in human lymphocytes after radiation and T-cell acute lymphoblastic leukemia
Authors: Cheng Zhenbo , Wang Yupeng , Guo Lihuang , Li Jiancheng , Zhang Wei , Zhang Conghui , Liu Yangxu , Huang Yue , Xu Keqian
Published: August 2022

Background

As one of the most common chromosomal causes, chromosome translocation leads to T-cell acute lymphoblastic leukemia (T-ALL). Ku70 is one of the key factors of error-prone DNA repair and it may end in translocation. So far, the direct correlation between Ku70 and translocation has not been assessed. This study aimed to investigate the association between Ku70 and translocation in human lymphocytes after radiation and T-ALL.

Methods

Peripheral blood lymphocytes (PBLs) from volunteers and human lymphocyte cell line AHH-1 were irradiated with X-rays to form the chromosome translocations. Phytohemagglutinin (PHA) was used to stimulate lymphocytes. The frequency of translocation was detected by fluorescence in situ hybridization (FISH). Meanwhile, the expression of Ku70 was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. Furthermore, Ku70 interference, overexpression and chemical inhibition were used in AHH-1 cell lines to confirm the correlation. Finally, the expression of Ku70 in T-ALL samples with or without translocation was detected.

Results

The expression of Ku70 and frequencies of translocation were both significantly increased in PBLs after being irradiated by X-rays, and a positive correlation between the expression (both mRNA and protein level) of Ku70 and the frequency of translocation was detected (r = 0.4877, P = 0.004; r = 0.3038, P = 0.0358 respectively). Moreover, Ku70 interference decreased the frequency of translocations, while the frequency of translocations was not significantly affected after Ku70 overexpression. The expression of Ku70 and frequencies of translocation were both significantly increased in cells after irradiation, combined with chemical inhibition (P < 0.01). The protein level and mRNA level of Ku70 in T-ALL with translocation were obviously higher than T-ALL with normal karyotype (P = 0.009, P = 0.049 respectively).

Conclusions

Ku70 is closely associated with the frequency of chromosome translocation in human lymphocytes after radiation and T-ALL. Ku70 might be a radiation damage biomarker and a potential tumor therapy target.
Medial pivot prosthesis has a better functional score and lower complication rate than posterior-stabilized prosthesis: a systematic review and meta-analysis
Authors: Shi Weipeng , Jiang Yaping , Wang Yingzhen , Zhao Xuan , Yu Tengbo , Li Tao
Published: August 2022

Purpose

We aimed to compare the postoperative clinical efficacy and safety of medial pivot (MP) prosthesis and posterior-stabilized (PS) prosthesis in the treatment of knee osteoarthritis (KOA).

Methods

All studies involving MP and PS prosthesis in PubMed, EMBASE, Cochrane Library, and Web of Science were searched since the establishment of the database. The included outcomes were knee range of motion (ROM), functional score, radiographic results, complication rate, and revision rate. Studies were independently evaluated by the Newcastle–Ottawa Scale for case–control studies and the assessment tool of the Cochrane Collaboration for randomized controlled trials. I2 was used to test the heterogeneity, and fixed- or random-effects models were selected for meta-analysis according to the heterogeneity results.

Results

A total of 19 studies, consisting of 3592 patients and 3783 knees (MP: 1811 knees, PS: 1972 knees), were included in the meta-analysis. The WOMAC (MD = − 1.11, 95% CI − 1.98 to − 0.23; P = 0.01) and HSS (MD = − 4.32, 95% CI − 8.30 to − 0.34; P = 0.03) in the MP group were significantly lower compared with the PS group, and the complication rate (OR 0.53, 95% CI 0.33–0.87; P = 0.01) was also lower compared with the PS group. There was no significant difference in ROM, radiographic results, and revision rate between the two groups (P > 0.5).

Conclusions

The existing literature provided evidence to support better clinical effect and lower complication rate of MP prosthesis compared to PS prosthesis. These results provide a reference for clinicians when choosing a suitable prosthesis.
Ischiofemoral impingement syndrome: a case report and review of literature
Authors: Jeyaraman Madhan , Murugan Jayanth , Maffulli Nicola , Jeyaraman Naveen , Potty Anish G. , Gupta Ashim
Published: August 2022

Introduction

The etiology of ischiofemoral impingement (IFI) syndrome, an unusual and uncommon form of hip pain, remains uncertain. Some patients demonstrate narrowing of the space between the ischial tuberosity and lesser trochanter from trauma or abnormal morphology of the quadratus femoris muscle. Combined clinical and imaging aid in the diagnosis.

Case report

A 32-year-old female presented with a 3 years history of pain over the lower aspect of the right buttock, aggravated by movements of the right hip, and partially relieved with rest and medications. The right hip showed extreme restriction of abduction and external rotation. MRI of the right hip showed reduced ischiofemoral space and quadratus femoris space when compared to the left hip. The patient underwent endoscopic resection of the right lesser trochanter, with no recurrence of pain at 2 years.

Conclusion

An unusual cause of hip pain, IFI syndrome, should be suspected when hip pain at extremes of movement is associated with signal abnormality of quadratus femoris muscle. Management is tailored to address the inciting factors that precipitated the IFI syndrome.
CircARID1A binds to IGF2BP3 in gastric cancer and promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA–protein ternary complex
Authors: Ma Qiang , Yang Feifei , Huang Bo , Pan Xiaojuan , Li Wei , Yu Ting , Wang Xiaolin , Ran Lingyu , Qian Kun , Li Hui , Li Haiping , Liu Yuying , Liang Ce , Ren Junwu , Zhang Yuying , Wang Shimin , Xiao Bin
Published: August 2022

Background

Gastric cancer (GC) is one of the most common malignant tumors in China. Circular RNAs (circRNAs) are novel non-coding RNAs with important regulatory roles in cancer progression. IGF2BP3 has been found to play oncogenic roles in various cancers including GC, while the exact mechanism of IGF2BP3 is largely unknown.

Methods

The expression of IGF2BP3 in GC was evaluated by Western Blot and bioinformatics analysis. CircRNA expression profiles were screened via IGF2BP3 RIP-seq in GC. Sanger sequencing, RNase R digestion, nucleo-plasmic separation and RNA-FISH assays were used to detect the existence and expression of circARID1A. RNA ISH assay was employed to test the expression of circARID1A in paraffin-embedded GC tissues. Moreover, the function of circARID1A on cellular proliferation was assessed by CCK-8, plate colony formation, EdU assays and GC xenograft mouse model in vivo. Furthermore, the location or binding of circARID1A, IGF2BP3 protein and SLC7A5 in GC was evaluated by RNA-FISH/IF or RNA pull-down assays.

Results

We identified a novel circRNA, circARID1A, that can bind to IGF2BP3 protein. CircARID1A was significantly upregulated in GC tissues compared with noncancerous tissues and positively correlated with tumor length, tumor volume, and TNM stage. CircARID1A knockdown inhibited the proliferation of GC cellsin vitroandin vivoand circARID1A played an important role in the oncogenic function of IGF2BP3. Mechanistically, circARID1A served as a scaffold to facilitate the interaction between IGF2BP3 and SLC7A5 mRNA, finally increasing SLC7A5 mRNA stability. Additionally, circARID1A was able to directly bind SLC7A5 mRNA through complementary base-pairing and then formed the circARID1A-IGF2BP3-SLC7A5 RNA–protein ternary complex and promoted the proliferation of GC via regulating AKT/mTOR pathway.

Conclusions

Altogether, our data suggest that circARID1A is involved in the function of IGF2BP3 and GC proliferation, and the circARID1A-IGF2BP3-SLC7A5 axis has the potential to serve as a novel therapeutic target for GC.
Can we get out of the COVID pandemic without adequate vaccination coverage in the pediatric population?
Authors: Esposito Susanna , Giordano Rosanna , Paini Giulia , Puntoni Matteo , Principi Nicola , Caminiti Caterina
Published: August 2022

Background

During the first and second COVID-19 pandemic waves, children, despite susceptible to SARS-CoV-2 infection, appeared at lower risk of severe disease, hospitalization, and death than adults and the elderly. Moreover, they seemed to play a minor role in the diffusion of the virus. The aim of this manuscript is to show epidemiological surveillance on COVID-19 incidence and hospitalization in the pediatric cohort in order to explain the importance of an adequate COVID-19 vaccination coverage in the pediatric population.

Methods

All subjects with documented SARS-CoV-2 infection diagnosed in Parma, Italy, between February 21st, 2020, and January, 31st, 2022, were recruited in this epidemiological surveillance. Diagnosis of infection was established in presence of at least one respiratory specimen positive for SARS-CoV-2 nucleic acid using a validated real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR) assay.

Results

The number of COVID-19 pediatric cases remained very low and lower than that recorded in the general population between early February 2020 and the end of October 2021, despite in the last part of this period the Delta variant emerged. On the contrary, starting from November 2021, a sharp and significant increase in COVID-19 incidence in the pediatric population was evidenced. This was detected in all the age groups, although greater in the populations aged 5–11 and 12–17 years old. Interestingly, the peak in hospitalization rate was observed in children < 5 years old, for whom COVID-19 vaccination is not approved yet. At the beginning of November 2021 among people older than 18 years of age 85.7% had completed the primary series of COVID-19 vaccine. Almost all the infants and pre-school children were susceptible. Until January 31st, 2022, 80.4% of adolescents aged 11–17 years had received at least two doses of COVID-19 vaccine and only 52.4% received the booster. Among children 5–11 years old, on January 31st, 2022, only 28.5% had received at least one vaccine dose.

Conclusions

Compared with adults and the elderly, presently a greater proportion of children and adolescents is susceptible to SARS-CoV-2 and could play a relevant role for the prolongation of the COVID-19 pandemic. Only a rapid increase in vaccination coverage of the pediatric populations can effectively counter this problem.
The impact of urbanization and wealth on house dust mite sensitization in children from north-central Nigeria
Authors: Zuiani Chiara , Arigliani Michele , Zubair Ramatu , Dogara Livingstone Gayus , Castriotta Luigi , Sunday Ashel Dache , Audu Reward Christopher , Dadan-Garba Habibah , Sani Zakary , Inusa Baba , Cogo Paola
Published: August 2022

The impact of socio-economic status on the risk of allergy in African children is not clear.

This was a cross sectional study including children aged 6–14 years from urban and rural settings in north-central Nigeria. Participants underwent skin prick tests to house dust mite (HDM) and an interview investigating socio-economic status through the Family Affluence Scale (FAS) based on a score of 0–6.

A total of 346 children were enrolled (52.8% boys; mean age ± SD 9.6 ± 2.0 years), including 142 (41% of total) rural and 204 (59% of total) urban pupils. Prevalence of HDM sensitivity was 2.8% (4/142) in the rural setting and 15.6% (32/204) in the urban setting (P < 0.001). Among urban children, frequency of HDM sensitization was 8.6% (7/81) in the lowest socio-economic group (FAS 0–1), 13.1% (8/61) in the intermediate one (FAS 2–3) and 27.4% (17/62) in the highest one (FAS ≥ 4).

Urbanization and increasing wealth are associated with a higher frequency of sensitization to HDM in Nigerian children.
Extended-release pharmacotherapy for opioid use disorder (EXPO): protocol for an open-label randomised controlled trial of the effectiveness and cost-effectiveness of injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone
Authors: Marsden John , Kelleher Mike , Hoare Zoë , Hughes Dyfrig , Bisla Jatinder , Cape Angela , Cowden Fiona , Day Edward , Dewhurst Jonathan , Evans Rachel , Hearn Andrea , Kelly Joanna , Lowry Natalie , McCusker Martin , Murphy Caroline , Murray Robert , Myton Tracey , Quarshie Sophie , Scott Gemma , Turner Sophie , Vanderwaal Rob , Wareham April , Gilvarry Eilish , Mitcheson Luke
Published: August 2022

Background

Sublingual tablet buprenorphine (BUP-SL) and oral liquid methadone (MET) are the daily, standard-of-care (SOC) opioid agonist treatment medications for opioid use disorder (OUD). A sizable proportion of the OUD treatment population is not exposed to sufficient treatment to attain the desired clinical benefit. Two promising therapeutic technologies address this deficit: long-acting injectable buprenorphine and personalised psychosocial interventions (PSI). This study will determine (A) the effectiveness and cost-effectiveness — monthly injectable, extended-release (BUP-XR) in a head-to-head comparison with BUP-SL and MET, and (B) the effectiveness of BUP-XR with adjunctive PSI versus BUP-SL and MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery from OUD will be also evaluated.

Methods

This is a pragmatic, multi-centre, open-label, parallel-group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five National Health Service community treatment centres in England and Scotland. At each centre, participants will be randomly allocated (1:1) to BUP-XR or SOC. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI or SOC with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from non-medical opioids during study weeks 2–24 combined with up to 12 urine drug screen tests for opioids. For 90% power (alpha, 5%; 15% inflation for attrition), 304 participants are needed for the BUP-XR versus SOC comparison. With the same planning parameters, 300 participants are needed for the BUP-XR and PSI versus SOC and PSI comparison. Statistical and health economic analysis plans will be published before data-lock on the Open Science Framework. Findings will be reported in accordance with the Consolidated Standards of Reporting Trials and Consolidated Health Economic Evaluation Reporting Standards.

Discussion

This pragmatic randomised controlled trial is the first evaluation of injectable BUP-XR versus the SOC medications BUP-SL and MET, with personalised PSI. If there is evidence for the superiority of BUP-XR over SOC medication, study findings will have substantial implications for OUD clinical practice and treatment policy in the UK and elsewhere.

Trial registration

EU Clinical Trials register 2018-004460-63.