bluuebunny/crossref_metadata_2025 huggingface dataset:
Job Satisfaction Among Psychomotor Physiotherapists in Norway
Authors: Rosenberg Marte Kimo , Bonsaksen Tore
Published: September 2022

The objective of the study was to investigate (i) levels of job satisfaction among employed and self-employed psychomotor physiotherapists in Norway and (ii) factors associated with job satisfaction. Although there are several studies on job satisfaction among physiotherapists, there is limited knowledge about job satisfaction among psychomotor physiotherapists in Norway. A cross-sectional survey was distributed to Norwegian psychomotor physiotherapists (n = 64) via a weblink. Job satisfaction was measured with 2 different scales (Warr’s and Speakman’s Job Satisfaction Scales). Group differences were analyzed with chi-squared tests and independent sample t-tests. Adjusted associations with job satisfaction were analyzed with multivariate linear regression. Fifty-eight women (90.6%) and 6 men (9.4%) were included in the study. The results revealed an overall high level of job satisfaction among the participants. None of the independent variables were associated with ratings on Warr’s Job Satisfaction Scale. When using Speakman’s Job Satisfaction Scale as outcome, employed practitioners had a higher level of job satisfaction, compared to their self-employed counterparts ( P < .01). Being employed was associated with a higher level of job satisfaction, compared to being self-employed. Self-employed physiotherapists also felt more overworked and experienced the job to be more physically demanding than their counterparts.
Stability delay margin computation of multi-area load frequency control system with electric vehicle using critical eigenvalue tracing method
Authors: Aydin Ömer , Sönmez Şahin , Ayasun Saffet
Published: September 2022

This work presents the delay-dependent stability analysis using eigenvalue tracing method for the multi-area load frequency control system that includes both electric vehicles aggregator (LFC-EVs) and incommensurate time delays in each control area. The LFC-EVs systems face inevitable communication time delays that affect the frequency stability. Although communication infrastructures are necessary to maintain system stability and reliability, a large amount of delay exceeding the allowable limit leads to system instability. In this study, stability delay margin values of a time-delayed LFC-EVs system are computed by a simple method finding the critical eigenvalues. By tracing eigenvalue loci of a transformation matrix, the method easily determines critical eigenvalues on the imaginary axis and obtains stability regions in time delay space. Stability delay margins depicted as a stability region in the delay space are determined for various system parameters and verified by time-domain simulations. Results indicate that more accurate stability delay margins are obtained as compared to ones using Lyapunov–Krasovskii Functionals with different linear matrix inequalities.
Discordance among assays for monitoring? Anticoagulation during extracorporeal life support
Authors: Scott Erik J , Rotar Evan , Dahl Jolian J , Beller Jared P , Money Dustin T , Chancellor W Z , Mehaffey J H , Morisette Matt , Yarboro Leora T , Teman Nicholas R
Published: September 2022

Objectives

The optimal method for monitoring of anticoagulation in patients on extracorporeal life support (ECLS) is unknown. The objective of this study was to assess the relationship between anti-factor Xa level (anti-Xa; IU/mL) and activated partial thromboplastin time (aPTT; seconds) for monitoring intravenous unfractionated heparin anticoagulation in adult ECLS patients.

Methods

Charts of all adult patients cannulated for ECLS from 2015 through 2017 were reviewed and laboratory and heparin infusion data were extracted for analysis. Time matched pairs of anti-Xa and aPTT were considered concordant if both laboratory values were within the same clinically utilized range. A hierarchical logistic regression model was used to determine factors associated with discordance while accounting for patient level effects.

Results

A total of 1016 paired anti-Xa and aPTT values from 65 patients were evaluated. 500 (49.2%) paired samples were discordant with a degree of variability on linear regression ( r 2 = 0.315). The aPTT fell into a higher therapeutic range compared to the anti-Xa in 31.6% and lower in 17.3%. Logistic regression demonstrated that discordance was independently associated with time from initiation of ECLS (OR 1.17 per day, p < 0.001), average heparin infusion rate (OR 1.25 per U/kg/hr, p < 0.001), and INR (OR 3.22, p < 0.001).

Conclusions

Nearly half of all aPTT and anti-Xa values were in discordant ranges and discordance is more likely as the time on ECLS and the INR level increase. The use of either assay in isolation to guide heparin anticoagulation may lead to misestimation of the degree of anticoagulation in complex ECLS patients.
Seismic response control of building structures under pulse-type ground motions by active vibration controller
Authors: Elias Said , Djerouni Salah , De Domenico Dario , Abdeddaim Mahdi , El Ouni Mohamed Hechmi
Published: September 2022

Active vibration control systems are commonly reported to be the most robust and effective method for vibration control of structures. However, the type of ground motions and the type of analysis may greatly influence their performances. This study investigates the seismic response of building with and without an active controller under pulse-type ground motions. A 20-story non-linear steel benchmark building is considered. Linear and non-linear analysis is conducted to check the effectiveness of the active control system. Active control with a linear quadratic Gaussian (LQG) control algorithm is applied to the benchmark building for seismic control purposes. Initially, some ground motions are selected following earlier studies from the literature concerning the benchmark building. It is found that the LQG control algorithm is quite effective under the considered earthquakes, and the analysis type does not affect the effectiveness of the controller. Thereafter, a set of additional 69 pulse-type ground motions are considered to check the performance of the LQG control algorithm and to find the suitability of linear analysis. It is noticed that under such pulse-type ground motion, the LQG control algorithm is not much effective if the non-linear behavior of the structure is incorporated in the seismic analysis, whereas in case of linear analysis, the LQG control algorithm is still effective. It is concluded that neglecting the non-linear behavior may lead to unconservative estimates of the seismic response when performing seismic analysis and designing structures equipped with active vibration control systems.
Fibro-Adipose Vascular Anomaly: Characteristic Imaging Features on Sonography and Magnetic Resonance Imaging
Authors: Hu WenJia , Gong YuBin , Ma JingJing , Wu Gang
Published: September 2022

Objective

To analyse the image characteristics of fibro-adipose vascular anomaly (FAVA) and the value of ultrasound and magnetic resonance imaging (MRI) for its diagnosis.

Methods

The clinical and imaging data characteristics of 10 patients with FAVA admitted to our hospital between January 2018 and December 2020 who underwent ultrasound and MRI diagnosis were retrospectively analysed.

Results

A total of 10 patients (six males and four females) with pathologically confirmed FAVA, aged from 3 to 27 years (median: 13 years), underwent ultrasound and MRI; of these, two patients underwent MRI-enhanced examinations. All lesions involved mainly muscle, with a few disruptions and involvements of subcutaneous fat. Five cases were located subcutaneously near the fascia; one case was adjacent to the periosteum. Ultrasound showed fascial tail in seven cases, and MRI showed fascial tail in six cases. Both ultrasound and MRI showed the lesions to be oval-shaped masses with blurred borders and a mean maximum diameter of 99.8 ± 48.7 mm. Ultrasound showed a mass with a mixture of high and low echoic areas. Magnetic resonance imaging imaging showed a heterogeneous, mixed-signal intensity on T1-weighted images, probably influenced by the fibrous and fatty components of the lesion. T2-weighted images showed a mixed-high signal. Enhanced computed tomography scans showed significant heterogeneous enhancement of the lesions.

Conclusion

Both ultrasound and MRI showed that fascial tail sign is an important imaging feature for FAVA disease; this provides a reliable basis for its diagnosis and can be used to distinguish it from venous malformations, which have no fascial tail signs. Therefore, fascial tail signs can be used as imaging features and require special attention in the diagnosis of FAVA disease.
Negotiating Stigma: Narratives of Displaced Children of the Kuki–Naga Ethnic Conf lict
Authors: Haokip Seilienmang
Published: September 2022

The Kuki–Naga ethnic conflict of the nineties marked a period of violence and displacement of large number of people. While the literature of this conflict expound the causes and spectacle nature of violence, the less visible impact, including the challenges of displacement and poverty induced by the separation from home, are always ignored. Through in-depth interviews among Kuki youth with childhood experiences of the violence and displacement, this article is an attempt to understand the harsh realities of displaced survivors of the violence and the everyday challenges as they began to rebuild their lives. Childhood memories of participants in the study reveal that stigmatisation of displaced persons imposed a strong degree of obstacle to their adjustment with the difficult transformation imposed by violence and displacement. Against this continuing threat to their daily experiences, this article argues that a strong sense of resilience can be adopted through inter-generational transmission of memories.
Use of the Straight Retrograde Intramedullary Nail for Tibiotalocalcaneal Arthrodesis: A Single-Institution, Single-Surgeon, Single-Implant Retrospective Series
Authors: Phillips McLeod , Bullock Garrett , Scott Aaron
Published: September 2022

Background:

The hindfoot fusion nail has become a popular implant for tibiotalocalcaneal (TTC) arthrodeses given its rigidity, ease of insertion, and potential for less invasive surgical approaches. The purpose of this study was to evaluate fusion and complication rates following the use of a straight, retrograde intramedullary nail for TTC arthrodeses, and the influence of diabetes and smoking on these results.

Methods:

A review of patient cases performed by a single surgeon at a single institution was performed. Variables included age, comorbidities, smoking history, BMI, hemoglobin A1c, preoperative and postoperative visual analog scale pain scores, assessment of healing, and complications. Relative and absolute risk were assessed for smoking, diabetes, fusion, and surgical complications through risk ratios. Cox proportional hazards survival analyses were performed to assess the effects of smoking and diabetes on fusion rates and complications. Linear regressions were performed to investigate the effects of smoking and diabetes on patient-reported pain levels.

Results:

Of 103 patients, there were 37 cigarette smokers and 30 diabetic patients. Eighty-three patients achieved union of all involved joints and 19 patients achieved union of 1 or 2 joints. Smokers demonstrated a 1.46 (risk ratio) (95% CI 1.03-2.07) times greater risk of nonunion but were not at an increased risk of experiencing surgical complications (0.86, 95% CI 0.56-1.33). Diabetic patients did not demonstrate an increased risk of nonunion (0.86, 95% CI 0.56-1.33) or complications (1.18, 95% CI 0.76-1.83).

Conclusion:

Because of increased nonunion risk, patients undergoing elective tibiotalocalcaneal arthrodesis should be counseled increased nonunion risks associated with smoking. In this series, we did not find a relationship between diabetes and complications or nonunion.

Level of Evidence:

Level III, retrospective cohort study.
pHisPred: a tool for the identification of histidine phosphorylation sites by integrating amino acid patterns and properties
Authors: Zhao Jian , Zhuang Minhui , Liu Jingjing , Zhang Meng , Zeng Cong , Jiang Bin , Wu Jing , Song Xiaofeng
Published: September 2022

Background

Protein histidine phosphorylation (pHis) plays critical roles in prokaryotic signal transduction pathways and various eukaryotic cellular processes. It is estimated to account for 6–10% of the phosphoproteome, however only hundreds of pHis sites have been discovered to date. Due to the inherent disadvantages of experimental methods, it is an urgent task for developing efficient computational approaches to identify pHis sites.

Results

Here, we present a novel tool, pHisPred, for accurately identifying pHis sites from protein sequences. We manually collected the largest number of experimental validated pHis sites to build benchmark datasets. Using randomized tenfold CV, the weighted SVM-RBF model shows the best performance than other four commonly used classification models (LR, KNN, RF, and MLP). From ten thousands of features, 140 and 150 most informative features were individually selected out for eukaryotic and prokaryotic models. The average AUC and F1-score values of pHisPred were (0.81, 0.40) and (0.78, 0.46) for tenfold CV on the eukaryotic and prokaryotic training datasets, respectively. In addition, pHisPred significantly outperforms other tools on testing datasets, in particular on the eukaryotic one.

Conclusion

We implemented a python program of pHisPred, which is freely available for non-commercial use at https://github.com/xiaofengsong/pHisPred. Moreover, users can use it to train new models with their own data.
Prevalence of pain and its association with quality of life of patients with heart failure in a developing country: findings from a multicenter cross-sectional study
Authors: Mhesin Deema , Nazzal Hadeel , Amerah Jalilah , Azamtta Murad , Ismail Yahia , Daralammouri Yunis , Abdalla Mazen A. , Jaber Mohammad M. , Koni Amer A. , Zyoud Sa’ed H.
Published: September 2022

Background

Heart failure (HF) is considered one of the main causes of morbidity and death among chronic diseases worldwide. Patients have increasingly reported chronic pain in long-standing heart failure as a disturbing symptom. Its unknown etiology and mechanism, in addition to its insidious progressive nature, made both the doctor and the patient not notice it until it affects the quality of life (QoL) and general health status. The primary objective of this study is to find the prevalence of pain in chronic heart failure patients and its impact on their QoL. The secondary objective is to determine the predictors of QoL in HF patients.

Methods

A multicenter cross-sectional design was used. The European Quality of Life scale five dimensions scale and the Brief Pain Inventory were adopted to evaluate QoL and pain, respectively. The Statistical Package for the Social Sciences version 25 was applied to present the data. The Mann-Whitney U, Kruskal-Wallis, and Cronbach alpha tests were used.

Results

The final study had a total of 142 individuals. The prevalence of pain among HF patients was 84.5%. Knee pain was the main complaint among patients. Our patients' median pain severity score was 18 [5.00–25.00], while the median pain interference score was 39 [24.75–53.00]. They had a median EQ-5D score of 0.34 [0.0–0.6] and an EQ-VAS score of 50 [30–70]. Pain severity (p = 0.004 andp < 0.001, respectively) and pain interference (p < 0.001 andp = 0.001, respectively) were found to significantly associated with both QoL scores; the visual analogue scale (EQ-VAS) and EQ-5D-5L. In multivariate analysis, monthly income was the only variable significantly correlated with EQ-VAS and EQ-5D-5L, along with pain variables.

Conclusions

Pain is a common symptom among patients with HF and is significantly associated with their QoL. Low income is also highly associated with poor QoL. Definitive guidelines should be achieved to increase awareness and understanding of the importance of pain management, reaching a higher QoL level, less pain, and good adherence to HF medications.
Validating ORR and PFS as surrogate endpoints in phase II and III clinical trials for NSCLC patients: difference exists in the strength of surrogacy in various trial settings
Authors: Hua Tiantian , Gao Yuan , Zhang Ruyang , Wei Yongyue , Chen Feng
Published: September 2022

Objective

This study aims to systematically validate the performance of surrogate endpoints in phase II and III clinical trials for NSCLC patients under various trial settings.

Methods

A literature search retrieved all registered phase II and III trials of NSCLC patients in which OS, with at least one of ORR and PFS, were reported. Associations between surrogate and true endpoints were assessed on two levels. On the arm level, three pairs of correlations, i.e., ORR vs. median OS, ORR vs. median PFS, and median PFS vs. median OS, were analysed using Spearman’s rho. On the trial level, similarly, three pairs of correlations, i.e., ΔORR vs. HR of OS, ΔORR vs. HR of PFS, and HR of PFS vs. HR of OS, were analysed using Spearman’s rho and weighted linear regression model respectively. Finally, sensitivity analyses were performed to explore surrogacy under various trial settings.

Results

At arm level, three pairs of correlations are all high (Spearman’s rho = 0.700, 0.831, 0.755, respectively). At trial level, there is a low correlation between ΔORR and HR of OS, a high correlation between ΔORR and HR of PFS and a moderate correlation between HR of PFS and HR of OS (Spearman’s rho = 0.462, 0.764, 0.584, respectively). In the sensitivity analysis, we find correlations between surrogate and true endpoints vary by different trial settings. It is noteworthy that the strength of surrogacy of these intermediate endpoints in targeted therapy is greater than that in immunotherapy.

Conclusion

According to the arm-level and trial level-analysis, we suggest that in phase II and III trials of targeted therapy and immunotherapy for NSCLC patients: 1) ORR lacks validity for the surrogacy of OS, excluding in first-line therapy, and 2) ORR may be an appropriate surrogate endpoint for PFS, and 3) PFS may be considered a modest surrogacy for OS, with better performance in first-line therapy trials. Moreover, to provide more convincing evidence of surrogacy of the surrogate endpoints, patient-level analyses are in desperate need.
An exploration into physician and surgeon data sensemaking: a qualitative systematic review using thematic synthesis
Authors: Whitelock-Wainwright Emma , Koh Jia Wei , Whitelock-Wainwright Alexander , Talic Stella , Rankin David , Gašević Dragan
Published: September 2022

Providing electronic health data to medical practitioners to reflect on their performance can lead to improved clinical performance and quality of care. Understanding the sensemaking process that is enacted when practitioners are presented with such data is vital to ensure an improvement in performance. Thus, the primary objective of this research was to explore physician and surgeon sensemaking when presented with electronic health data associated with their clinical performance. A systematic literature review was conducted to analyse qualitative research that explored physicians and surgeons experiences with electronic health data associated with their clinical performance published between January 2010 and March 2022. Included articles were assessed for quality, thematically synthesised, and discussed from the perspective of sensemaking. The initial search strategy for this review returned 8,829 articles that were screened at title and abstract level. Subsequent screening found 11 articles that met the eligibility criteria and were retained for analyses. Two articles met all of the standards within the chosen quality assessment (Standards for Reporting Qualitative Research, SRQR). Thematic synthesis generated five overarching themes: data communication, performance reflection, infrastructure, data quality, and risks. The confidence of such findings is reported using CERQual (Confidence in the Evidence from Reviews of Qualitative research). The way the data is communicated can impact sensemaking which has implications on what is learned and has impact on future performance. Many factors including data accuracy, validity, infrastructure, culture can also impact sensemaking and have ramifications on future practice. Providing data in order to support performance reflection is not without risks, both behavioural and affective. The latter of which can impact the practitioner’s ability to effectively make sense of the data. An important consideration when data is presented with the intent to improve performance.

Registration This systematic review was registered with Prospero, registration number: CRD42020197392.
Atheroprone fluid shear stress-regulated ALK1-Endoglin-SMAD signaling originates from early endosomes
Authors: Mendez Paul-Lennard , Obendorf Leon , Jatzlau Jerome , Burdzinski Wiktor , Reichenbach Maria , Nageswaran Vanasa , Haghikia Arash , Stangl Verena , Hiepen Christian , Knaus Petra
Published: September 2022

Background

Fluid shear stress enhances endothelial SMAD1/5 signaling via the BMP9-bound ALK1 receptor complex supported by the co-receptor Endoglin. While moderate SMAD1/5 activation is required to maintain endothelial quiescence, excessive SMAD1/5 signaling promotes endothelial dysfunction. Increased BMP signaling participates in endothelial-to-mesenchymal transition and inflammation culminating in vascular diseases such as atherosclerosis. While the function of Endoglin has so far been described under picomolar concentrations of BMP9 and short-term shear application, we investigated Endoglin under physiological BMP9 and long-term pathophysiological shear conditions.

Results

We report here that knock-down of Endoglin leads to exacerbated SMAD1/5 phosphorylation and atheroprone gene expression profile in HUVECs sheared for 24 h. Making use of the ligand-trap ALK1-Fc, we furthermore show that this increase is dependent on BMP9/10. Mechanistically, we reveal that long-term exposure of ECs to low laminar shear stress leads to enhanced Endoglin expression and endocytosis of Endoglin in Caveolin-1-positive early endosomes. In these endosomes, we could localize the ALK1-Endoglin complex, labeled BMP9 as well as SMAD1, highlighting Caveolin-1 vesicles as a SMAD signaling compartment in cells exposed to low atheroprone laminar shear stress.

Conclusions

We identified Endoglin to be essential in preventing excessive activation of SMAD1/5 under physiological flow conditions and Caveolin-1-positive early endosomes as a new flow-regulated signaling compartment for BMP9-ALK1-Endoglin signaling axis in atheroprone flow conditions.
Impact of community and provider-driven social accountability interventions on contraceptive uptake in Ghana and Tanzania
Authors: Steyn Petrus S. , Cordero Joanna Paula , Nai Dela , Shamba Donat , Fuseini Kamil , Mrema Sigilbert , Habib Ndema , Nguyen My Huong , Kiarie James
Published: September 2022

Background

Social accountability, which is defined as a collective process for holding duty bearers and service providers to account for their actions, has shown positive outcomes in addressing the interrelated barriers to quality sexual and reproductive health services. The Community and Provider driven Social Accountability Intervention (CaPSAI) Project contributes to the evidence on the effects of social accountability processes in the context of a family planning and contraceptive programme.

Methods

A quasi-experimental study utilizing an interrupted time series design with a control group (ITS-CG) was conducted to determine the actual number of new users of contraception amongst women 15–49 years old in eight intervention and eight control facilities per country in Ghana and Tanzania. A standardized facility audit questionnaire was used to collect facility data and completed every year in both intervention and control groups in each country from 2018–2020.

Results

In Ghana, the two-segmented Poisson Generalized Estimating Equation (GEE) model demonstrated no statistically significant difference at post-intervention, between the intervention and control facilities, in the level of uptake of contraceptives (excess level) (p-value = 0.07) or in the rate of change (excess rate) in uptake (p-value = 0.07) after adjusting for baseline differences. Similarly, in Tanzania, there was no statistical difference between intervention and control facilities, in the level of uptake of contraceptives (excess level) (p-value = 0.20), with the rate of change in uptake (p-value = 0.05) after adjusting for the baseline differences. There was no statistical difference in the level of or rate of change in uptake in the two groups in a sensitivity analysis excluding new users recruited in outreach activities in Tanzania.

Conclusions

The CAPSAI project intervention did not result in a statistically significant increase in uptake of contraceptives as measured by the number of or increase in new users. In evaluating the impact of the intervention on the intermediate outcomes such as self-efficacy among service users, trust and countervailing power among social groups/networks, and responsiveness of service providers, cases of change and process evaluation should be considered.

Trial registration

The CaPSAI Project has been registered at the Australian New Zealand Clinical Trials Registry (ACTRN12619000378123, 11/03/2019).
Desmoid-type fibromatosis in the setting of malignant peritoneal mesothelioma: a case report of two rare diseases
Authors: Gregory Stephanie N. , Satterwhite Audra A. , Alexander H. Richard , Blakely Andrew M.
Published: September 2022

Background

Desmoid-type fibromatosis (DTF) is a rare benign lesion that usually arises from the abdominal wall or extremities and rarely from the mesentery or intrabdominal organs. Malignant peritoneal mesothelioma is also a rare, yet aggressive disease. To our knowledge, this is the first case report of desmoid-type fibromatosis in the setting of malignant peritoneal mesothelioma.

Case presentation

An early 30-year-old female was referred to our center for large intra-abdominal mass concerning for recurrent malignant peritoneal mesothelioma after previous cytoreductive surgery with hyperthermic intraperitoneal chemotherapy and adjuvant chemotherapy. Further investigation revealed a large mesenteric mass, which was resected en bloc with the cecum and terminal ileum. Pathologic findings confirmed a surprising diagnosis of desmoid-type fibromatosis.

Conclusions

No adjuvant therapy was offered to this patient due to negative tumor margins; however, close follow-up will be provided for recurrence of both malignant peritoneal mesothelioma and desmoid-type fibromatosis, which can be differentiated in the future via biopsy in this patient.
Psychometric properties of the Chinese version of the Positive Thinking Scale in individuals after hip fracture surgery
Authors: Chien Ching-Hui , Huang Yi-Wen
Published: September 2022

Positive thinking is a form of positive cognition and a coping strategy. The Positive Thinking Scale (PTS) is used to measure positive thinking, but the reliability and validity of the PTS-Chinese have yet to be tested. This study aims to examine the psychometric properties of the PTS-Chinese. A total of 154 patients post-hip fracture surgery completed the questionnaire in a hospital in Taiwan between April 2020 and December 2020. The scales in the questionnaire included the PTS, Automatic Thoughts Questionnaire-Positive, Automatic Thoughts Questionnaire-Negative, Barthel Index, and items related to happiness, demographics, and disease treatment. The results of the confirmatory factor analysis and average variance extracted show that the PTS-Chinese version exhibits construct validity. Scores on the PTS-Chinese version are positively related to scores on the Automatic Thoughts Questionnaire-Positive and happiness items and negatively related to scores on the Automatic Thoughts Questionnaire-Negative. This finding indicates that the PTS-Chinese demonstrates concurrent, predictive, and discriminant validity. The scale also presents acceptable reliability and test–retest reliability. Overall, the PTS-Chinese can be used to evaluate and track the positive thinking of patients. Further studies are needed to assess the psychometric properties of the PTS-Chinese in different cultures and ethnic groups.
Three-dimensional bioprinting of mucoadhesive scaffolds for the treatment of oral mucosal lesions; an in vitro study
Authors: Koopaie Maryam , Nassar Duha Hayder Mohammad Ali , Shokrolahi Mahvash
Published: September 2022

Background

Chronic oral lesions could be a part of some diseases, including mucocutaneous diseases, immunobullous diseases, gastrointestinal diseases, and graft versus host diseases. Systemic steroids are an effective treatment, but they cause unfavorable and even severe systemic side effects. Discontinuation of systemic corticosteroids or other immunosuppressive drugs leads to relapse, confirming the importance of long-term corticosteroid use. The present study aims to fabricate a mucoadhesive scaffold using three-dimensional (3D) bioprinting for sustained drug delivery in oral mucosal lesions to address the clinical need for alternative treatment, especially for those who do not respond to routine therapy.

Methods

3D bioprinting method was used for the fabrication of the scaffolds. Scaffolds were fabricated in three layers; adhesive/drug-containing, backing, and middle layers. For evaluation of the release profile of the drug, artificial saliva was used as the release medium. Mucoadhesive scaffolds were analyzed using a scanning electron microscope (SEM) and SEM surface reconstruction. The pH of mucoadhesive scaffolds and swelling efficacy were measured using a pH meter and Enslin dipositive, respectively. A microprocessor force gauge was used for the measurement of tensile strength. For the evaluation of the cytotoxicity, oral keratinocyte cells' survival rate was evaluated by the MTT method. Folding endurance tests were performed using a stable microsystem texture analyzer and analytic probe mini tensile grips.

Results

All scaffolds had the same drug release trend; An initial rapid explosive release during the first 12 h, followed by a gradual release. The scaffolds showed sustained drug release and continued until the fourth day. The pH of the surface of the scaffolds was 5.3–6.3, and the rate of swelling after 5 h was 28 ± 3.2%. The tensile strength of the scaffolds containing the drug was 7.8 ± 0.12 MPa. The scaffolds were non-irritant to the mucosa, and the folding endurance of the scaffolds was over three hundred times.

Conclusion

The scaffold fabricated using the 3D bioprinting method could be suitable for treating oral mucosal lesions.
Osteoporosis clinical practice guideline: romosozumab for treating severe osteoporosis – an update by the Egyptian Academy of Bone Health
Authors: Miedany Yasser El , Gadallah Naglaa Ali , Toth Mathias , Hassan Waleed , Elgaafary Maha , Hassan Mohamed , Eissa Mervat , Saber Sally , Elwakil Walaa , Mahran Safaa
Published: September 2022

Background

This is a Clinical Practice Guideline update released by the Egyptian Academy of Bone Health and Metabolic Bone Diseases. It does not replace the clinical practice guidelines published for the treatment of osteoporosis in 2021, but it entails specific recommendations and selective criteria for romosozumab as another pharmacological agent for treatment of postmenopausal osteoporosis. It has been issued, in part, due to the imminent approval of romosozumab in Egypt.

Main text

The guideline recommends the use of romosozumab, for up to 1 year, for the reduction of vertebral, hip, and non-vertebral fractures in postmenopausal women with severe osteoporosis at very high risk of fracture/imminent fracture risk: defined as T-score less than − 2.5 and a prior hip or vertebral fracture in the past 24 months or a very high fracture risk, as identified by FRAX (FRAX major osteoporosis fracture > 30%, FRAX hip fracture > 4.5%). The recommended dosage of romosozumab is 210 mg monthly by subcutaneous injection for 12 months. For osteoporotic postmenopausal women who have completed a 12-month course of romosozumab, treatment with an anti-resorptive osteoporosis therapy is recommended to maintain bone mineral density gains and reduce fracture risk. The treatment is not recommended for women at high risk of cardiovascular disease and stroke, which includes those with prior myocardial infarction or stroke.

In conclusion, strategies to osteoporosis management have been highly diversified, with bone health specialists have become able to set up treatment plan tailored to the individual patient’s requirement. Patients with severe osteoporosis at very high fracture risk need stronger therapeutic regimens to start with. Romosozumab endorses bone formation and suppresses bone resorption, leading to a greater anabolic window and a superior positive impact on bone mineral density.
Thrombopoietin enhances neutrophil production by bone marrow hematopoietic progenitors with the aid of stem cell factor in congenital neutropenia
Authors: Sawai Nobukuni , Koike Kenichi , Mwamtemi Hadija Hemed , Ito Susumu , Kurokawa Yumi , Sakashita Kazuo , Kinoshita Tatsuya , Higuchi Tsukasa , Takeuchi Kouichi , Shiohara Masaaki , Kamijo Takehiko , Higuchi Yumiko , Miyazaki Hiroshi , Kato Takashi , Kobayashi Masao , Miyake Munenori , Yasui Kozo , Komiyama Atsushi
Published: September 2022

We examined the effects of granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), and thrombopoietin (TPO), alone or in combination, on the generation of neutrophils by bone marrow (BM) cells from three patients with severe congenital neutropenia (SCN) through the use of a serum-deprived liquid culture system. Synergistic effects of G-CSF and SCF on the neutrophil production by BM CD34+CD38+c-kit+ cells were observed in SCN patients as well as in normal controls. The addition of TPO to the culture containing G-CSF and SCF further augmented the growth of neutrophils in the two groups. Single-cell culture experiments revealed that the three-factor combination caused increases in both the number and size of neutrophil colonies compared with G-CSF + SCF in normal BM cells, whereas only a significant increment in the colony size was observed in SCN patients. Even in the presence of SCF or SCF + TPO, the concentrations of G-CSF necessary for the substantial production of neutrophils by CD34+CD38+c-kit+ cells were higher in two patients compared with the levels obtained by normal control cells. In addition, TPO did not accelerate the maturation of neutrophilic cells supported by G-CSF + SCF. When BM CD34+CD38−c-kit+ cells were targeted, the addition of TPO to the culture containing G-CSF and SCF was required for significant neutrophil colony growth in the two groups. These results suggest that TPO enhances the G-CSF-dependent neutrophil production with the aid of SCF in this disorder.
HIV-1 replication in CD4+ T cell lines: the effects of adaptation on co-receptor use, tropism, and accessory gene function
Authors: Dejucq Nathalie
Published: September 2022

We studied the replication of HIV-1 macrophage-tropic CCR5-using strains (R5) in CD4+ T cell lines to better understand the switch in co-receptor use of such strains during disease progression and to assess resulting changes in cell tropism. We found that the majority of R5 strains cannot replicate in CD4+ T cell lines without adaptation by serial passage. A small minority of primary R5 isolates, however, were able to infect two T cell lines, Molt4 and SupT1. This expanded tropism was due to the use of undetectable levels of CCR5 rather than CXCR4 or alternative receptors. In contrast, HIV-1SF162 adaptation for replication in the C8166 T cell line was due to the emergence of variant strains that could use CXCR4. Of two variants, one was dual-tropic and one T-tropic, although both could use CCR5 as well as CXCR4. A single mutation in the start codon of the accessory gene vpu accounted for the T-tropic phenotype of the second variant, indicating that a non-functional vpu impairs macrophage tropism. Thus, in vitro and in the absence of an immune response, R5 strains naturally adapt to infect CXCR4+ T cell lines. Such adaptation resembles the rare R5 to X4 switch that occurs in vivo. Mutations in accessory genes (e.g., vpu) not required for replication in rapidly dividing cell lines may also occur in vitro, abrogating replication in primary cell types such as macrophages. Such mutations, however, are normally selected against in vivo.
Proinflammatory response and IL-12 expression in HIV-1 infection
Authors: Ma Xiaojing , Montaner Luis J
Published: September 2022

HIV-1 infection elicits a broad range of host responses, many of which interfere with the regulatory pathways of gene expression of interleukin-12 (IL-12), a heterodimeric cytokine essential for cell-mediated immunity against microbial infection. The inhibition of IL-12 production by accessory cells after HIV-1 infection has been identified as a potential factor responsible for impaired innate and Th1 cell-mediated responses observed in AIDS patients. The mechanism by which HIV-1 infection suppresses IL-12 gene expression is largely uncharacterized. Here we review all pathways identified that could potentially mediate HIV-induced impairment of IL-12 gene expression, such as IL-10, transforming growth factor β, interferon-α/β, tumor necrosis factor α, Fc receptors, complement regulatory proteins, and receptors. Also discussed is the decreased CD40 ligand induction in CD4 T cells during HIV infection, which may have a strong impact on T cell-dependent IL-12 production that is critical for the establishment and maintenance of a Th1 response.
Sequential migration of neutrophils across monolayers of endothelial and epithelial cells
Authors: Mul Frederik P J , Zuurbier Astrid E M , Janssen Hans , Calafat Jero , van Wetering Sandra , Hiemstra Pieter S , Roos Dirk , Hordijk Peter L
Published: September 2022

In the course of granulocyte-dominated lung inflammation, granulocytes migrate across the endothelium and epithelium of the lung and cause severe tissue damage. To study this process in more detail, we developed a bilayer transmigration model composed of primary human endothelial and lung epithelial cells, simultaneously cultured on opposite sides of Transwell filters. Electron microscopical analysis showed that the morphology of the cells and the expression of junctional proteins remained unaltered and that matrix components were deposited onto the filter. Intriguingly, neutrophil migration was more efficient across the bilayers than across single epithelial monolayers and did not differ from migration across single endothelial monolayers. Coculture experiments showed that endothelial cells stimulated epithelial cells to release IL-6 and that epithelial cells enhanced release of IL-8 from endothelial cells. Together these data reveal bidirectional signaling and enhanced neutrophil migration in a transmigration model of primary human epithelial and endothelial cells.
Clustering on the forward surfaces of migrating neutrophils of a novel GPI-anchored protein that may regulate neutrophil adherence and migration
Authors: Nakamura-Sato Yukiko , Sasaki Katsunori , Watanabe Hiroshi , Araki Yoshihiko , Sendo Fujiro
Published: September 2022

We previously reported a novel glycosylphosphatidylinositol (GPI)-anchored glycoprotein (tentatively designated GPI-80) on human leukocytes that may be involved in the regulation of neutrophil adherence and migration. In this study, we examined by immuno- and scanning electron microscopy, the distribution of GPI-80 on neutrophil surfaces. GPI-80 was diffusely distributed on the surface of resting neutrophils and on the peripheral areas of adherent cells after stimulation with N-formyl-methionyl-leucyl-phenylalanine. After longer stimulation (60 min), GPI-80 decreased in number and was again diffusely distributed on the surfaces of round neutrophils. Few GPI-80 were detected on the ventral surfaces of adherent neutrophils. Clusters of GPI-80 were detected on the forward surfaces of neutrophils transmigrating through pores of nitrocellulose membranes. These results may give a morphological background of possible role of GPI-80 for neutrophil extravasation.
Adenoviral transduction of human E-selectin into isolated, perfused, rat aortic segments: anex vivomodel for studying leukocyte-endothelial interactions
Authors: Ishii Hideto , Yoshida Masayuki , Rosenzweig Anthony , Gimbrone Michael A , Yasukochi Yukio , Numano Fujio
Published: September 2022

E-selectin, a member of the selectin family of adhesion molecules, is thought to play an important role in leukocyte-endothelial (EC) interactions during inflammation and atherosclerosis. To critically examine the role of E-selectin in leukocyte-EC interactions in the vascular system, we created a recombinant adenoviral vector containing a human E-selectin cDNA (AdRSVE-sel) and examined the effect of AdRSVE-sel in an ex vivo vascular model of a rat aortic segment. A segment of abdominal aorta was isolated from a male Sprague-Dawley rat transduced with AdRSVE-sel ex vivo. After 72 h, surface expression of transduced E-selectin in the segment was confirmed by Western blotting and immunohistochemistry using anti-E-selectin mAb. Aortic segments were connected to a perfusion system and the adhesion of human polymorphonuclear neutrophils (PMN), and a human monocytic cell line (THP-1) to the EC surface was studied in the presence of a physiological level of flow (0.85 ml/min, approximate luminal surface shear stress=1.76 dyn/cm2). Adhesion of PMN was assessed by scanning electron microscopy and quantified using fluorescently labeled PMN. AdRSVE-sel transduced aortic segments mediated significantly more PMN and THP-1 adhesion than control segments transduced with AdRSVLacZ. Pretreatment of AdRSVE-sel transduced aortic segments with anti-E-selectin mAb inhibited PMN adhesion significantly, as well as THP-1. These data indicate that human E-selectin expressed in rat aortic segments can support the adhesion of human PMN as well as THP-1 under physiological flow conditions. This genetically modified, excised, vascular-segment model provides a useful tool for the study of leukocyte recruitment in the vascular system.
α-Melanocyte-stimulating hormone peptides inhibit HIV-1 expression in chronically infected promonocytic U1 cells and in acutely infected monocytes
Authors: Barcellini Wilma , Colombo Gualtiero , La Maestra Letteria , Clerici Giuliana , Garofalo Letizia , Brini Anna T , Lipton James M , Catania Anna
Published: September 2022

The purpose of the present research was to determine if α-melanocyte-stimulating hormone (α-MSH) and its C-terminal tripeptide [α-MSH (11–13), KPV] alter HIV expression in infected cells. The results indicate that chronically HIV-1-infected promonocytic U1 cells produce α-MSH and that immunoneutralization of the endogenous peptide enhances HIV expression. Because U1 cells express the α-MSH receptor 1 (MC1R), an autocrine-inhibitory circuit based on the peptide and its receptor likely occurs in these cells. To determine effects of pharmacological concentrations of α-MSH peptides on HIV expression, we measured p24 antigen release by TNF-α-stimulated U1 cells exposed to a wide range of concentrations of synthetic α-MSH and KPV. Viral expression was reduced by both peptides. KPV also effectively reduced HIV replication in acutely infected monocyte-derived macrophages (MDM). The basis of the peptide influence on viral replication is at the transcriptional level; KPV inhibited activation of NF-κB that is known to enhance viral expression. Endogenous α-MSH likely contributes to natural defense against HIV. However, greater concentrations of synthetic peptide are much more effective in reducing HIV expression in infected cells.
Identification of mature and immature human thymic dendritic cells that differentially express HLA-DR and interleukin-3 receptor in vivo
Authors: Schmitt Christian , Fohrer Hélène , Beaudet Sylvie , Palmer Pierre , Alpha Marie-José , Canque Bruno , Gluckman Jean Claude , Dalloul Ali H
Published: September 2022

We have previously shown that thymic CD34+ cells have a very limited myeloid differentiation capacity and differentiatein vitro mostly into CD1a+-derived but not CD14+-derived dendritic cells (DC). Herein we characterized the human neonatal thymic DC extracted from the organ in relationship with the DC generated from CD34+ cells in situ. We show that in vivo thymic DC express E cadherin, CLA, CD4, CD38, CD40, CD44, and granulocyte-macrophage colony-stimulating factor-R (GM-CSF-R; CD116) but no CD1a. According to their morphology, functions, and surface staining they could be separated into two distinct subpopulations: mature HLA-DRhi, mostly interleukin-3-R (CD123)-negative cells, associated with thymocytes, some apoptotic, and expressed myeloid and activation markers but no lymphoid markers. In contrast, immature HLA-DR+ CD123hi CD36+ cells with monocytoid morphology lacked activation and myeloid antigens but expressed lymphoid antigens. The latter express pTα mRNA, which is also found in CD34+ thymocytes and in blood CD123hi DC further linking this subset to lymphoid DC. However, the DC generated from CD34+ thymic progenitors under standard conditions were pTα-negative. Thymic lymphoid DC showed similar phenotype and cytokine production profile as blood/tonsillar lymphoid DC but responded to GM-CSF, and at variance with them produced no or little type I interferon upon infection with viruses and did not induce a strict polarization of naive T cells into TH2 cells. Their function in the thymus remains therefore to be elucidated.
Heterogeneity of human peripheral blood monocyte subsets
Authors: Grage-Griebenow E , Flad H-D , Ernst M
Published: September 2022

In recent years the number of reports describing phenotypically and functionally distinct subsets of human blood leukocytes, and in particular of subtypes of antigen-presenting cells has continuously increased. A great diversity was described not only for dendritic cells (DC), but also for human blood monocytes (Mo) and macrophages (Mac). Similar to DC, the different types of Mo subsets could be defined by distinct phenotypes and immunoregulatory functions. The characterization of blood Mo subpopulations revealed that some of them exhibit common features with myeloid or lymphoid DC and tissue Mac, but also demonstrate the existence of novel unique cell populations. The generation of lymphoid and myeloid DC and their heterogeneity has been the subject of recent reviews. Here we focus on Mo from human peripheral blood and summarize the data (including our own) dealing with their phenotypic and functional, in particular immunoregulatory properties.