Conceptualizing Scaffold Guided Breast Tissue Regeneration in a Preclinical Large Animal Model.

Scaffold-guided breast tissue regeneration (SGBTR) can transform both reconstructive and cosmetic breast surgery. Implant-based surgery is the most common method. However, there are inherent limitations, as it involves replacement of tissue rather than regeneration. Regenerating autologous soft tissue has the potential to provide a more like-for-like reconstruction with minimal morbidity. Our SGBTR approach regenerates soft tissue by implanting additively manufactured bioresorbable scaffolds filled with autologous fat graft. A pre-clinical large animal study was conducted by implanting 100 mL breast scaffolds (n = 55) made from medical-grade polycaprolactone into 11 minipigs for 12 months. Various treatment groups were investigated where immediate or delayed autologous fat graft, as well as platelet rich plasma, were added to the scaffolds. Computed tomography and magnetic resonance imaging were performed on explanted scaffolds to determine the volume and distribution of the regenerated tissue. Histological analysis was performed to confirm the tissue type. At 12 months, we were able to regenerate and sustain a mean soft tissue volume of 60.9 ± 4.5 mL (95% CI) across all treatment groups. There was no evidence of capsule formation. There were no immediate or long-term post-operative complications. In conclusion, we were able to regenerate clinically relevant soft tissue volumes utilizing SGBTR in a pre-clinical large animal model.

Validation and evaluation of school-based mental health literacy training program "The Guide Cymru" in Iranian adolescent students aged 13-15: study protocol.

BACKGROUND: Schools are an ideal setting for enhancing mental health literacy, a crucial strategy for improving adolescents' mental health knowledge and attitudes and promoting help-seeking. "The Guide Cymru" program is an adaptation of the mental health literacy program" The Guide" that was developed in Canada. The program will be culturally adapted for 13- to 15-year-old Iranian adolescent students in the first secondary schools. METHODS: In this randomized controlled trial, using the stratified random sampling procedure, the whole eighth and ninth grade student body (aged 13 to 15) from Sirjan City's first secondary schools will be included in the study. Twenty first secondary schools will be randomly assigned to one of two groups: control or intervention. Finally, 562 students and 40 teachers will participate in the research. The tools of mental health literacy scale (MHLs), mental health general knowledge and attitudes related to mental disorders/illnesses are employed in this study. DISCUSSION: This trial aims to be to explore whether "The Guide Cymru", a mental health literacy program offered to students as part of the school curriculum, can decrease the stigma associated with mental health and promote help-seeking behaviors among students.

Trastuzumab in patients with breast cancer and pre-existing left ventricular systolic dysfunction.

BACKGROUND: Trastuzumab is one of the most effective treatments in HER-2 positive breast cancer patients. However, it is associated with development of cardiomyopathy/heart failure (HF) which is often a limiting side effect and associated with overall adverse outcomes. As a result, patients with pre-existing LV systolic dysfunction (LVSD) are often excluded from receiving anti-HER-2 therapy, which may lead to less effective cancer treatment and worse prognosis. OBJECTIVES: The current study aims to evaluate the safety of trastuzumab in patients with HER-2 positive breast cancer and pre-existing LVSD. METHODS: In this retrospective cohort study, 36 consecutive patients at a single center in Iran with HER-2 positive breast cancer with asymptomatic mild LVSD with LVEF 40-53% without heart failure symptoms and those who were closely followed in the Cardio-Oncology clinic before initiating the treatment and then every two cycles of trastuzumab were included. As per the program standard protocol they received a beta-blocker (carvedilol) and ACE-I (Lisinopril), up to the maximum tolerated dose, if there were no contraindications. Patients underwent routine echocardiography with global longitudinal strain (GLS) assessment every 3 months per guideline recommendations and were followed up 6 months after the end of treatment. Primary composite outcomes included myocardial infarction (MI), cardiac arrhythmia, heart failure(HF) symptoms and cardiovascular death. Secondary outcome was ≥ 10% reduction in LVEF or ≥ 15% reduction in GLS compared to baseline. If the LVEF decreased below 40%, the treatment was temporarily interrupted for one or two cycles, and spironolactone was added to the patient's treatment. If the LVEF improved ≥ 40%, trastuzumab was rechallenged. Data analysis was performed using IBM SPSS Statistics 24.0. Software. Patients' characteristics were reported using descriptive statistics, and its association with drop in LVEF or GLS was assessed using Pearson chi-square or Mann-Whitney U test. A p-value of less than 0.05 was considered significant. RESULTS: Thirty-six patients were included in the study. Primary composite outcome was noted in 1(2.8%) patient. LVEF reduction of ≥ 10% occurred in 6(16.7%) of the patients, and a GLS reduction of more than 15% was detected in 4 (11.1%) of the patients. There was a significant association between a ≥ 10% reduction in LVEF and baseline systolic blood pressure (P-value: 0.04). LVEF reduction below 40% was observed in 3 (8.3%) patients, where trastuzumab was interrupted. All of these three patients had obesity (Median BMI 34.11, IQR 9.12) and uncontrolled HTN, and one of them had symptoms of heart failure (NYHA class II), for whom the trastuzumab treatment was discontinued. Among two patients, after the temporary interruption of trastuzumab, and addition of spironolactone, LVEF improved to above 40%, and the treatment was restarted with close cardiac monitoring; therefore, they could complete the entire one-year treatment period. CONCLUSIONS: Treatment with trastuzumab seems to be safe in patients with pre-existing LVSD (LVEF = 40-53%). Such high-risk patients should be strictly monitored and cardiovascular risk factors, such as HTN should be regulated.

Cardiac lipoma in a young lady.

Key Clinical Message: To confirm the diagnosis of cardiac lipomas, it is crucial to use multimodality imaging and also histopathology examination if the patient underwent surgery. But surgery is not needed in many cases unless there are life-threatening situations. Abstract: Cardiac lipoma is a rare condition which is believed as a benign tumor; here, we want to present a case of young adult lady who came to our hospital complaining of chest pain and diagnosed cardiac mass by echocardiography that underwent cardiac MRI which showed cardiac lipoma and managed conservatively by serial echocardiography.

Right ventricle toxicity in cancer treatment: a focused review on cardiac imaging.

Background: The right ventricle (RV) remains the 'forgotten chamber' in the clinical assessment of cancer therapy-related cardiac dysfunction (CTRCD). Aim: We aimed to review the role that various cardiac imaging modalities play in RV assessment as part of the integrative management of patients undergoing cancer therapy. Discussion: RV assessment remains challenging by traditional 2D echocardiography. In this review we discuss other parameters such as right atrial strain, and other echocardiographic modalities such as 3D and stress echocardiography. We also elaborate on the specific role that cardiac magnetic resonance imaging and equilibrium radionuclide angiocardiography can play in assessing the RV. Conclusion: Biventricular function should be monitored following chemotherapy for early detection of subclinical CTRCD and possible solitary RV changes.

Cancer is among the most common health concerns worldwide. In addition to cancer's effects itself on the body, chemotherapy agents and medication, drug treatments that use powerful chemicals to kill cancer cells, are putting further strain on individuals' bodies impairing their quality of life. Chemotherapy agents are a major risk factor for cardiac injuries by their cardiotoxic effects (the damage they cause to the heart). Previous studies have tried to find the earliest way of noticing cardiac changes in patients who are receiving special chemotherapy drugs. Most of the studies and definitions for this cardiotoxic event are limited to the assessment of left ventricles, one of the chambers of the heart that is involved in providing oxygenated blood to the body. However, there is some evidence that suggests the evaluation of the right ventricle, another chamber of the heart that pumps blood low in oxygen to the lungs, for faster notice. Having this insight can open new targets for cancer therapy-related cardiac dysfunction (CTRCD) prevention and therapy.

The role of biomechanical factors in models of intervertebral disc degeneration across multiple length scales.

Low back pain is the leading cause of disability, producing a substantial socio-economic burden on healthcare systems worldwide. Intervertebral disc (IVD) degeneration is a primary cause of lower back pain, and while regenerative therapies aimed at full functional recovery of the disc have been developed in recent years, no commercially available, approved devices or therapies for the regeneration of the IVD currently exist. In the development of these new approaches, numerous models for mechanical stimulation and preclinical assessment, including in vitro cell studies using microfluidics, ex vivo organ studies coupled with bioreactors and mechanical testing rigs, and in vivo testing in a variety of large and small animals, have emerged. These approaches have provided different capabilities, certainly improving the preclinical evaluation of these regenerative therapies, but challenges within the research environment, and compromises relating to non-representative mechanical stimulation and unrealistic test conditions, remain to be resolved. In this review, insights into the ideal characteristics of a disc model for the testing of IVD regenerative approaches are first assessed. Key learnings from in vivo, ex vivo, and in vitro IVD models under mechanical loading stimulation to date are presented alongside the merits and limitations of each model based on the physiological resemblance to the human IVD environment (biological and mechanical) as well as the possible feedback and output measurements for each approach. When moving from simplified in vitro models to ex vivo and in vivo approaches, the complexity increases resulting in less controllable models but providing a better representation of the physiological environment. Although cost, time, and ethical constraints are dependent on each approach, they escalate with the model complexity. These constraints are discussed and weighted as part of the characteristics of each model.

Mediastinal gray zone lymphoma in a pregnant woman presenting with cardiac tamponade.

BACKGROUND: Mediastinal gray zone lymphoma is a newly recognized rare B cell neoplasm, which is challenging in diagnosis and treatment. CASE PRESENTATION: In the current study, we aimed to report a 25-year-old pregnant woman at 25 weeks of gestation who presented with chronic cough and progressive shortness of breath, hypotension, tachycardia, and tachypnea. A large circumferential pericardial effusion with compressive effect on the right atrium and right ventricle and a large extracardiac mass with external pressure to mediastinal structures were seen on trans thoracic echocardiography. The emergency pericardiocentesis was performed with the diagnosis of cardiac tamponade. Also, CMR revealed a huge heterogeneous anterior mediastinal mass, and the pathology and the immunohistochemistry of the mass biopsy revealed gray zone lymphoma with positive CD3, CD20, CD30, CD45, PAX5, and negative CD15 expression. Three courses of chemotherapy with the CHOP regimen were performed with an acceptable response every three weeks before delivery. A caesarian section was performed at 37 weeks without any problem for the patient and fetus, and chemotherapy will be started three weeks after delivery. CONCLUSION: Cardiac tamponade as an emergency condition occurred in this pregnant patient by malignant pericardial effusion and mediastinal mass pressure. Accurate diagnosis and on time interventions caused a significant improvement and a successful delivery.

A Preclinical Animal Model for the Study of Scaffold-Guided Breast Tissue Engineering.

Scaffold-guided breast tissue engineering (SGBTE) has the potential to transform reconstructive breast surgery. Currently, there is a deficiency in clinically relevant animal models suitable for studying novel breast tissue engineering concepts. To date, only a small number of large animal studies have been conducted and characterization of these large animal models is poorly described in the literature. Addressing this gap in the literature, this publication comprehensively describes our original porcine model based on the current published literature and the experience gained from previous animal studies conducted by our research group. In a long-term experiment using our model, we investigated our SGBTE approach by implanting 60 additively manufactured bioresorbable scaffolds under the panniculus carnosus muscle along the flanks of 12 pigs over 12 months. Our model has the flexibility to compare multiple treatment modalities where we successfully investigated scaffolds filled with various treatments of immediate and delayed fat graft and augmentation with platelet rich plasma. No wound complications were observed using our animal model. We were able to grow clinically relevant volumes of soft tissue, which validates our model. Our preclinical large animal model is ideally suited to assess different scaffold or hydrogel-driven soft tissue regeneration strategies. Impact statement The ability to regenerate soft tissue through scaffold-guided tissue engineering concepts can transform breast reconstructive surgery. We describe an original preclinical large animal model to study controlled and reproducible scaffold-guided breast tissue engineering (SGBTE) concepts. This model features the flexibility to investigate multiple treatment conditions per animal, making it an efficient model. We have validated our model with a long-term experiment over 12 months, which exceeds other shorter published studies. Our SGBTE concept provides a more clinically relevant approach in terms of breast reconstruction. Future studies using this model will support the translation of SGBTE into clinical practice.

Sustaining the National Spinal Cord Injury Registry of Iran (NSCIR-IR) in a Regional Center: Challenges and Solutions.

BACKGROUND: The National Traumatic Spinal Cord Injury Registry in Iran (NSCIR-IR), was implemented initially in three hospitals as a pilot phase from 11 Oct 2015 to 19 Jun 2016 and has been active in eight centers from 19 Jun 2016. Poursina Hospital, a trauma care referral center in Rasht, Guilan Province of Iran is one of the registry sites, and has been involved in registering eligible patients since 1 Jan 2016. This study aimed to identify the challenges and solutions for sustaining the NSCIR-IR in a regional center. METHODS: This was a mixed-methods study. For the quantitative analysis, a retrospective observational design was used to measure case capture or case identification rate, mapping cases in the registry against those eligible for registry inclusion amongst the register of hospital admissions. For the qualitative component, data was collected using focus group discussions and semi-structured interviews, followed by thematic analysis. RESULTS: From 19 Jun 2016 to 24 Jan 2018, the proportion of case capture (case identification rate) was 17%. The median time between case identification and data entry to the system was 30.5 d (range: 2 to 193 d). Thematic analysis identified a lack of trained human resources as the most important cause of low case identification rate and delay in data completion. CONCLUSION: Recruitment and education to increase trained human resources are needed to improve case capture, the timeliness of data input and registry sustainability in a regional participating site.

Type II Photoinitiator and Tuneable Poly(Ethylene Glycol)-Based Materials Library for Visible Light Photolithography.

Stereolithography (SL) has several advantages over traditional biomanufacturing techniques such as fused deposition modeling, including increased speed, accuracy, and efficiency. While SL has been broadly used in tissue engineering for the fabrication of three-dimensional scaffolds that can mimic the in vivo environment for cell growth and tissue regeneration, lithographic printing is usually performed on single-component materials cured with ultraviolet light, severely limiting the versatility and cytocompatibility of such systems. In this study, we report a highly tunable, low-cost photoinitiator system that we used to establish a systematic library of crosslinked materials based on low molecular weight poly(ethylene glycol) diacrylate. We assessed the physicochemical properties, photocrosslinking efficiency, cost performance, and biocompatibility to demonstrate the capability of manufacturing a multimaterial complex tissue scaffold. [Figure: see text] Impact statement Stereolithography (SL) has advantages over traditional biomanufacturing techniques, including accuracy and efficiency. While SL has been broadly used for fabricating three-dimensional scaffolds that can mimic the in vivo environment for cell growth and tissue regeneration, lithographic printing is usually performed on single-component materials cured with ultraviolet light, severely limiting the versatility and cytocompatibility of such systems. In this study, we report a highly tunable photoinitiator system and establish a systematic library of crosslinked materials based on poly(ethylene glycol) diacrylate. We assessed the physicochemical properties, photocrosslinking efficiency and biocompatibility to demonstrate the capability of manufacturing a multimaterial complex tissue scaffold.

A comparative study of wound dressings loaded with silver sulfadiazine and silver nanoparticles: In vitro and in vivo evaluation.

In the current study, two series of antimicrobial dressings conjugated with silver sulfadiazine (SSD) and silver nanoparticles (AgNPs) were developed and evaluated for chronic wound healing. Highly porous polycaprolactone (PCL)/polyvinyl alcohol (PVA) nanofibers were loaded with different concentrations of SSD or AgNPs and compared comprehensively in vitro and in vivo. SSD and AgNPs indicated a strong and equal antimicrobial activity against S. aureus. However, SSD had more toxicity against fibroblast cells over one week in vitro culture. An in vivo model of wound healing on male Wistar rats was developed with a full thickness wound. All the wound dressings indicated enough flexibility and hydrophilicity, which resulted an adequate adhesion into the wound closure. After 30 days, the control group without any treatment indicated 31% wound closure while the group treated with PCL/PVA (without antimicrobial components) indicated 44% wound closure. Presence of antimicrobial components in the PCL/PVA nanofibers resulted into a lower inflammation response leading to a faster proliferation and maturation phases. In agreement with the higher biocompatibility of AgNPs than SSD, a faster angiogenesis, epithelialization and subsequently, remodeling were observed for the wound dressings loaded with AgNPs. The group treated with the highest concentration of AgNPs showed the fastest healing process leading to a final epithelialization with 96% wound closure after 30 days. This study indicated that AgNPs have higher biocompatibility and regulate wound healing process more efficiently compared to SSD. PCL/PVA nanofibers conjugated with AgNPs are promising wound dressings for full-thickness wounds.

Assessment of Care and its Associated Factors in Traumatic Patients in North of Iran.

OBJECTIVE: To determine the status of pre-hospital emergency care and its associated factors in traumatic patients. METHODS: In across-sectional study, 577 traumatic patients who were transferred to Poursina hospital by EMS (Emergency Medical Services) personnel were selected by simple random sampling method. Pre-hospital emergency services were observed. Then the mean of taken measures scores for each domain was determined in percent and evaluated in terms of associated factors (age, working experience of staff and number of missions per day) and compared using Spearman's test. RESULTS: Out of 577 patients, 454 were men (78.7%) and 123 women (21.3%). Their mean age was 35.1 years old. Accident (82.7%) was the most common mechanism of injury. Most vehicles involved in the accident were light -weight cars (48.5%) and motorcycles (32.2%). A significant relationship was found between age, general domain (p=0.039) and hemodynamic (p=0.019) as well as between work experience and general domain (p=0.018). CONCLUSION: Given that pre-hospital emergency services provided in most of the domains are relatively far from world standard, results of this research can provide information for managers to improve strategic planning on care and medical services, appropriation of budget, knowledge of personnel and necessary equipment.

Independent Evaluation of Medical-Grade Bioresorbable Filaments for Fused Deposition Modelling/Fused Filament Fabrication of Tissue Engineered Constructs.

Three-dimensional printing/additive manufacturing (3DP/AM) for tissue engineering and regenerative medicine (TE/RM) applications is a multifaceted research area encompassing biology, material science, engineering, and the clinical sciences. Although being quite mature as a research area, only a handful of clinical cases have been reported and even fewer commercial products have made it to the market. The regulatory pathway and costs associated with the introduction of bioresorbable materials for TE/RM have proven difficult to overcome, but greater access to 3DP/AM has spurred interest in the processing and availability of existing and new bioresorbable materials. For this purpose, herein, we introduce a series of medical-grade filaments for fused deposition modelling/fused filament fabrication (FDM/FFF) based on established and Federal Drug Administration (FDA)-approved polymers. Manufacturability, mechanical characterization, and accelerated degradation studies have been conducted to evaluate the suitability of each material for TE/RM applications. The comparative data serves to introduce these materials, as well as a benchmark to evaluate their potential in hard and soft tissue engineering from a physicochemical perspective.

Utilization of Molecular Dynamics Simulation Coupled with Experimental Assays to Optimize Biocompatibility of an Electrospun PCL/PVA Scaffold.

The main focus of this study is to address the possibility of using molecular dynamics (MD) simulation, as a computational framework, coupled with experimental assays, to optimize composite structures of a particular electrospun scaffold. To this aim, first, MD simulations were performed to obtain an initial theoretical insight into the capability of heterogeneous surfaces for protein adsorption. The surfaces were composed of six different blends of PVA (polyvinyl alcohol) and PCL (polycaprolactone) with completely unlike hydrophobicity. Next, MTT assay was performed on the electrospun scaffolds made from the same percentages of polymers as in MD models to gain an understanding of the correlation between protein adsorption on the composite surfaces and their capability for cell proliferation. To perform simulations, two ECM (extracellular matrix) protein fragments, namely, collagen type I and fibronectin, two essential proteins for initial cell attachment and eventual cell proliferation, were considered. To evaluate the strength of protein adsorption, adhesion energy and final conformations of proteins were studied. For MTT analysis, different blends of PCL/PVA electrospun scaffolds were prepared, on which endothelial cells were cultured for one week. Theoretical results indicated that the samples with more than 50% of PCL significantly represented stronger protein adsorption. In agreement with simulation results, experimental analysis also demonstrated that the more hydrophobic the surface became, the better initial cell attachment and cell proliferation could be achieved, which was particularly better observed in samples with more than 70% of PCL.

Antimicrobial Wound Dressing Containing Silver Sulfadiazine With High Biocompatibility: In Vitro Study.

Many patients all over the world suffer from acute wounds caused by traumas or burns. In most crucial cases, skin regeneration cannot be promoted spontaneously, and skin grafts are applied as the main treatment. However, this therapy has some drawbacks which motivate researchers to develop wound dressings. In this study, electrospun mats consisting of polycaprolactone (PCL) and polyvinyl alcohol (PVA) incorporated with silver sulfadiazine (SSD) are proposed to be used as antimicrobial wound dressings with the capability of cell seeding. Various amounts of SSD were loaded into PVA nanofibers, and the effects of SSD particles on the morphological characteristics of nanofibers, mechanical behaviors, and physical properties of the mats were studied for the first time. The cellular viability, antimicrobial properties of the scaffolds, and release behavior of silver were also examined. Finally, the best concentration of SSD was determined based on the quality of nanofibers, antibacterial features, and the ability of cellular attachment and proliferation. Fibronectin was also coated to enhance the biocompatibility of the selective scaffold. It was shown that the mats have appropriate mechanical properties with good handling ability in wet environment and also have a hydrophilic surface to adhere to the wound bed. Results indicate that SSD particles increase the fiber diameter and hydrophilic properties, while they weaken the mechanical characteristics of the mats. Furthermore, 5 wt% SSD/PVA was determined as the best concentration of SSD as it results in a desirable fiber quality for the mats with enough antimicrobial properties and acceptable cell proliferation on the surface. Coating fibronectin was also introduced as an effective method to increase the biocompatibility of the scaffolds incorporated with SSD particles.

Integrative Utilization of Microenvironments, Biomaterials and Computational Techniques for Advanced Tissue Engineering.

This review aims to propose the integrative implementation of microfluidic devices, biomaterials, and computational methods that can lead to a significant progress in tissue engineering and regenerative medicine researches. Simultaneous implementation of multiple techniques can be very helpful in addressing biological processes. Providing controllable biochemical and biomechanical cues within artificial extracellular matrix similar to in vivo conditions is crucial in tissue engineering and regenerative medicine researches. Microfluidic devices provide precise spatial and temporal control over cell microenvironment. Moreover, generation of accurate and controllable spatial and temporal gradients of biochemical factors is attainable inside microdevices. Since biomaterials with tunable properties are a worthwhile option to construct artificial extracellular matrix, in vitro platforms that simultaneously utilize natural, synthetic, or engineered biomaterials inside microfluidic devices are phenomenally advantageous to experimental studies in the field of tissue engineering. Additionally, collaboration between experimental and computational methods is a useful way to predict and understand mechanisms responsible for complex biological phenomena. Computational results can be verified by using experimental platforms. Computational methods can also broaden the understanding of the mechanisms behind the biological phenomena observed during experiments. Furthermore, computational methods are powerful tools to optimize the fabrication of microfluidic devices and biomaterials with specific features. Here we present a succinct review of the benefits of microfluidic devices, biomaterial, and computational methods in the case of tissue engineering and regeneration medicine. Furthermore, some breakthroughs in biological phenomena including the neuronal axon development, cancerous cell migration and blood vessel formation via angiogenesis by virtue of the aforementioned approaches are discussed.

Quality of life in patients with cutaneous leishmaniasis.

BACKGROUND: Leishmaniasis is a zoonotic infection caused by a protozoa belonging to the genus Leishmania. Its clinical manifestations range from a self-healing cutaneous leishmaniasis (CL) to lethal visceral leishmaniasis. We aim to examine the quality of life of patients with CL in Kerman, Iran.  METHODS: In this cross-sectional study we evaluated 124 patients with CL. The Dermatology Life Quality Index (DLQI) questionnaire was used for measuring quality of life. Data on demographics and characteristics of the lesions also were collected. Mann-Whitney U-test and Kruskal-Wallis were used for data analyses. RESULTS: The mean DLQI score was 5.87 ± 5.96. We observed the highest effect in the symptoms and feelings domains; the lowest effect was seen in the treatment domain of the DLQI. There was no significant difference in DLQI scores between men and women. Patients with ulcerated lesions had lower quality of life (P < 0.05).  CONCLUSION: CL significantly affects the quality of life of patients. Further studies are suggested to examine the effect of its treatment on the quality of life in these patients.