Association between waterpipe smoking and lung cancer: a multicentre case-control study in Iran.

OBJECTIVES: This study investigated the association between lung cancer and waterpipe smoking, which is an emerging global public health concern. STUDY DESIGN: Multicentre case-control study. METHODS: This study included 627 cases and 3477 controls from the Iranian Study of Opium and Cancer (IROPICAN) study, which was conducted between 2017 and 2020. One frequency-matched control for each lung cancer patient was selected by age, gender and residential place; however, this study used controls of four cancer types in the analyses. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence intervals (CIs). Additional analyses were performed among 181 lung cancer cases and 2141 controls who were not cigarette smokers or opium or nass/pipe users. RESULTS: The odds of lung cancer were higher among waterpipe smokers than never-smokers (OR = 1.3, 95% CI: 1.0-1.7). Results showed a higher OR of lung cancer for those who smoked the waterpipe daily (OR = 2.1, 95% CI: 1.4-3.0), smoked more than two heads per day (OR = 2.7, 95% CI: 1.8-4.0), had smoked for >20 years (OR = 1.9, 95% CI: 1.3-2.7), smoked more than 20 head-years (OR = 2.8, 95% CI: 1.9-4.1) and initiated smoking before the age of 30 years (OR = 1.7, 95% CI: 1.1-2.5). The association was only statistically significant for squamous cell carcinomas (OR = 1.8, 95% CI 1.2-2.7). Furthermore, this study observed a higher OR of lung cancer among exclusive waterpipe smokers (OR = 2.3, 95% CI: 1.6, 3.5). CONCLUSIONS: Waterpipe smoking was associated with an increased risk of lung cancer. The association was stronger with higher frequency, duration and intensity of exposure to waterpipe smoking. The association increases in exclusive waterpipe smokers, which is likely due to controlling for residual confounding by cigarette smoking and opium consumption, and higher exposure levels in this subpopulation.

An indentation-based framework for probing the glycosaminoglycan-mediated interactions of collagen fibrils.

Microscale deformation processes, such as reorientation, buckling, and sliding of collagen fibrils, determine the mechanical behavior and function of collagenous tissue. While changes in the structure and composition of tendon have been extensively studied, the deformation mechanisms that modulate the interaction of extracellular matrix (ECM) constituents are not well understood, partly due to the lack of appropriate techniques to probe the behavior. In particular, the role of glycosaminoglycans (GAGs) in modulating collagen fibril interactions has remained controversial. Some studies suggest that GAGs act as crosslinkers between the collagen fibrils, while others have not found such evidence and postulate that GAGs have other functions. Here, we introduce a new framework, relying on orientation-dependent indentation behavior of tissue and computational modeling, to evaluate the shear-mediated function of GAGs in modulating the collagen fibril interactions at a length scale more relevant to fibrils compared to bulk tests. Specifically, we use chondroitinase ABC to enzymatically deplete the GAGs in tendon; measure the orientation-dependent indentation response in transverse and longitudinal orientations; and infer the microscale deformation mechanisms and function of GAGs from a microstructural computational model and a modified shear-lag model. We validate the modeling approach experimentally and show that GAGs facilitate collagen fibril sliding with minimal crosslinking function. We suggest that the molecular reconfiguration of GAGs is a potential mechanism for their microscale, strain-dependent viscoelastic behavior. This study reveals the mechanisms that control the orientation-dependent indentation response by affecting the shear deformation and provides new insights into the mechanical function of GAGs and collagen crosslinkers in collagenous tissue.

Orientation-dependent indentation reveals the crosslink-mediated deformation mechanisms of collagen fibrils.

The spatial arrangement and interactions of the extracellular matrix (ECM) components control the mechanical behavior of tissue at multiple length scales. Changes in microscale deformation mechanisms affect tissue function and are often hallmarks of remodeling and disease. Despite their importance, the deformation mechanisms that modulate the mechanical behavior of collagenous tissue, particularly in indentation and compression modes of deformation, remain poorly understood. Here, we develop an integrated computational and experimental approach to investigate the deformation mechanisms of collagenous tissue at the microscale. While the complex deformation arising from indentation with a spherical probe is often considered a pitfall rather than an opportunity, we leverage this orientation-dependent deformation to examine the shear-regulated interactions of collagen fibrils and the role of crosslinks in modulating these interactions. We specifically examine tendon and cervix, two tissues rich in collagen with quite different microstructures and mechanical functions. We find that interacting, crosslinked collagen fibrils resist microscale longitudinal compressive forces, while widely used constitutive models fail to capture this behavior. The reorientation of collagen fibrils tunes the compressive stiffness of complex tissues like cervix. This study offers new insights into the mechanical behavior of collagen fibrils during indentation, and more generally, under longitudinal compressive forces, and illustrates the mechanisms that contribute to the experimentally observed orientation-dependent mechanical behavior. STATEMENT OF SIGNIFICANCE: Remodeling and disease can affect the deformation and interaction of tissue constituents, and thus mechanical function of tissue. Yet, the microscale deformation mechanisms are not well characterized in many tissues. Here, we develop a combined experimental-computational approach to infer the microscale deformation mechanisms of collagenous tissues with very different functions: tendon and cervix. Results show that collagen fibrils resist microscale forces along their length, though widely-used constitutive models do not account for this mechanism. This deformation process partially modulates the compressive stiffness of complex tissues such as cervix. Computational modeling shows that crosslink-mediated shear deformations are central to this unexpected behavior. This study offers new insights into the deformation mechanisms of collagenous tissue and the function of collagen crosslinkers.

Clinical long-term results of radial head arthroplasty in comminuted radial head fractures.

Modern radial head prostheses have recently become more common in the treatment of comminuted radial head fractures. The goal of this study was to evaluate how well the EVOLVE® modular metallic radial head implant prosthetic restores the functional range of motion and stability of the elbow. 30 patients with comminuted radial head fractures received an arthroplasty with an EVOLVE® prosthesis in our institution. 20 of those patients were available for long-term follow-up (mean > 10 years). The outcomes were assessed on the basis of pain, motion, and strength. The overall outcome was scored with functional rating scores. According to the Broberg-Morrey elbow evaluation score, after a mean follow-up period of 10.2 years, ten (50.0%) patients were rated as very good, four (20.0%) as good, six (30.0%) as satisfactory, and none as poor. In the long-term results the Broberg-Morrey score increased from 79 (in short-term results) to 89 points. The Disabilities of the Arm, Shoulder, and Hand (DASH) outcome measure questionnaire showed an average of 16.2 points. Initially, patients had an extension deficit of 20°, which was reduced to 5° at the latest follow-up. In our long-term results, an improvement in the function of the elbow was observed after arthroplasty using a metallic modular radial head implant. Comminuted radial head fractures with elbow instability can be treated effectively with the EVOLVE® radial head prosthesis, which restores stability in acute treatment. Our long-term results after 10.2 years demonstrate good functional outcome and low major complication rate. IV.

Improved electron trajectory and power distribution in APPLE-knot undulator.

The APPLE-Knot undulator has been proposed to reduce the large on-axis heat load of the APPLE-II at very low photon energy. However, the current designs have an inherent non-zero second field integral due to the Knot sections, resulting in a transverse deflection of the electron beam throughout the undulator. For a long device, such a deviation can degrade the brightness and power distribution of the outgoing beam. Here, a new end-Knot section is presented to compensate for the electron trajectory, and the undulator is symmetrized to balance the output power distribution. The performance of the APPLE-Knot with symmetric power distribution is investigated. The partial power, flux, and polarization are compared with the APPLE-II. In the linear mode, APPLE-Knot shows a pronounced reduction of the partial power, with a similar flux to the APPLE-II. The symmetric power density distribution reduces the hotspot by 41%, with a flux loss of less than 5%. In the circular mode and at low photon energies, the flux is limited by the phase error of the symmetric design.

Heterogeneous microstructural changes of the cervix influence cervical funneling.

The cervix acts as a dynamic barrier between the uterus and vagina, retaining the fetus during pregnancy and allowing birth at term. Critical to this function, the physical properties of the cervix change, or remodel, but abnormal remodeling can lead to preterm birth (PTB). Although cervical remodeling has been studied, the complex 3D cervical microstructure has not been well-characterized. In this complex, dynamic, and heterogeneous tissue microenvironment, the microstructural changes are likely also heterogeneous. Using quantitative, 3D, second-harmonic generation microscopy, we demonstrate that rat cervical remodeling during pregnancy is not uniform across the cervix; the collagen fibers orient progressively more perpendicular to the cervical canals in the inner cervical zone, but do not reorient in other regions. Furthermore, regions that are microstructurally distinct early in pregnancy become more similar as pregnancy progresses. We use a finite element simulation to show that heterogeneous regional changes influence cervical funneling, an important marker of increased risk for PTB; the internal cervical os shows ∼6.5x larger radial displacement when fibers in the inner cervical zone are parallel to the cervical canals compared to when fibers are perpendicular to the canals. Our results provide new insights into the microstructural and tissue-level cervical changes that have been correlated with PTB and motivate further clinical studies exploring the origins of cervical funneling. STATEMENT OF SIGNIFICANCE: Cervical funneling, or dilation of the internal cervical os, is highly associated with increased risk of preterm birth. This study explores the 3D microstructural changes of the rat cervix during pregnancy and illustrates how these changes influence cervical funneling, assuming similar evolution in rats and humans. Quantitative imaging showed that microstructural remodeling during pregnancy is nonuniform across cervical regions and that initially distinct regions become more similar. We report, for the first time, that remodeling of the inner cervical zone can influence the dilation of the internal cervical os and allow the cervix to stay closed despite increased intrauterine pressure. Our results suggest a possible relationship between the microstructural changes of this zone and cervical funneling, motivating further clinical investigations.

Use of an Intramedullary Locking Nail for the Treatment of Patella Fractures.

PURPOSE OF THE STUDY Treatment of patella fractures has always been difficult; especially in older patients. The aim of this study was to investigate the XS nail in the treatment of patella fractures. MATERIAL AND METHODS 49 fractures could be registered and reevaluated with a standardized questionnaire. RESULTS Mean follow-up time was 38.67 months, mean age 71.48 years. The mean OKS was 16.26 points, the Kujala Score was 81.56 points. No wound healing or revision could be detected. CONCLUSIONS The XS nail is a good treatment option with a low risk of complications also for the age-related trauma patient and for more complex patella fractures. Key words: patella, patella fracture, XS nail, locking nail, intramedullary nail, nail osteosynthesis.

Molybdenum trioxide enhances viability, osteogenic differentiation and extracellular matrix formation of human bone marrow-derived mesenchymal stromal cells.

BACKGROUND: Metals and their ions allow specific modifications of the biological properties of bioactive materials that are intended for application in bone tissue engineering. While there is some evidence about the impact of particles derived from orthopedic Cobalt-Chromium-Molybdenum (Co-Cr-Mo) alloys on cells, there is only limited data regarding the influence of the essential trace element Mo and its ions on the viability, osteogenic differentiation as well as on the formation and maturation of the primitive extracellular matrix (ECM) of primary human bone marrow-derived stromal cells (BMSCs) available so far. METHODS: In this study, the influence of a wide range of molybdenum (VI) trioxide (MoO3), concentrations on BMSC viability was evaluated via measurement of fluorescein diacetate metabolization. Thereafter, the impact of three non-cytotoxic concentrations of MoO3 on the cellular osteogenic differentiation as well as on ECM formation and maturation of BMSCs was assessed. RESULTS: MoO3 had no negative influence on BMSC viability in most tested concentrations, as viability was in fact even enhanced. Only the highest concentration (10 mM) of MoO3 showed cytotoxic effects. Cellular osteogenic differentiation, measured via the marker enzyme alkaline phosphatase was enhanced by the presence of MoO3 in a concentration-dependent manner. Furthermore, MoO3 showed a positive influence on the expression of relevant marker genes for osteogenic differentiation (osteopontin, osteocalcin and type I collagen alpha 1) and on the formation and maturation of the primitive ECM, as measured by collagen deposition and ECM calcification. CONCLUSION: MoO3 is considered as an attractive candidate for supplementation in biomaterials and qualifies for further research.

The role of dimensionality and geometry in quench-induced nonequilibrium forces.

We present an analytical formalism, supported by numerical simulations, for studying forces that act on curved walls following temperature quenches of the surrounding ideal Brownian fluid. We show that, for curved surfaces, the post-quench forces initially evolve rapidly to an extremal value, whereafter they approach their steady state value algebraically in time. In contrast to the previously-studied case of flat boundaries (lines or planes), the algebraic decay for curved geometries depends on the dimension of the system. Specifically, steady-state values of the force are approached in time ast-d/2ind-dimensional spherical (curved) geometries. For systems consisting of concentric circles or spheres, the exponent does not change for the force on the outer circle or sphere. However, the force exerted on the inner circles or sphere experiences an overshoot and, as a result, does not evolve to the steady state in a simple algebraic manner. The extremal value of the force also depends on the dimension of the system, and originates from curved boundaries and the fact that particles inside a sphere or circle are locally more confined, and diffuse less freely than particles outside the circle or sphere.

A Systematic Review and Meta-analysis of the Medical Error Rate in Iran: 2005-2019.

BACKGROUND AND OBJECTIVES: Medical errors (MEs) are one of the main factors affecting the quality of hospital services and reducing patient safety in health care systems, especially in developing countries. The aim of this study was to determine the rate of ME in Iran. METHODS: This is a systematic literature review and meta-analysis of extracted data. The databases MEDLINE, EMBASE, Scopus, Cochrane, SID, Magiran, and Medlib were searched in Persian and English, using a combination of medical subject heading terms ("Medical Error" [Mesh] OR "Medication error" [Mesh] OR "Hospital Error" AND ("Iran" [Mesh]) for observational and interventional studies that reported ME rate in Iran from January 1995 to April 2019. We followed the STROBE checklist for the purpose of this review. RESULTS: The search yielded a total of 435 records, of which 74 articles were included in the systematic review. The rate of MEs in Iran was determined as 0.35%. The rates of errors among physicians and nurses were 31% and 37%, respectively. The error rates during the medication process, including prescription, recording, and administration, were 31%, 27%, and 35%, respectively. Also, incidence of MEs in night shifts was higher than in any other shift (odds ratio [OR] = 38%; 95% confidence interval [CI]: 31%-45%). Moreover, newer nurses were responsible for more errors within hospitals than other nurses (OR = 57%; 95% CI: 41%-80%). The rate of reported error after the Health Transformation Plan was higher than before the Health Transformation Plan (OR = 40%; CI: 33%-49% vs OR = 30%; CI: 25%-35%). CONCLUSION: This systematic review has demonstrated the high ME rate in Iranian hospitals. Based on the error rate attributed solely to night shifts, more attention to the holistic treatment process is required. Errors can be decreased through a variety of strategies, such as training clinical and support staff regarding safe practices and updating and adapting systems and technologies.

An optomechanogram for assessment of the structural and mechanical properties of tissues.

The structural and mechanical properties of tissue and the interplay between them play a critical role in tissue function. We introduce the optomechanogram, a combined quantitative and qualitative visualization of spatially co-registered measurements of the microstructural and micromechanical properties of any tissue. Our approach relies on the co-registration of two independent platforms, second-harmonic generation (SHG) microscopy for quantitative assessment of 3D collagen-fiber microstructural organization, and nanoindentation (NI) for local micromechanical properties. We experimentally validate our method by applying to uterine cervix tissue, which exhibits structural and mechanical complexity. We find statistically significant agreement between the micromechanical and microstructural data, and confirm that the distinct tissue regions are distinguishable using either the SHG or NI measurements. Our method could potentially be used for research in pregnancy maintenance, mechanobiological studies of tissues and their constitutive modeling and more generally for the optomechanical metrology of materials.

Ionic dissolution products of Cerium-doped bioactive glass nanoparticles promote cellular osteogenic differentiation and extracellular matrix formation of human bone marrow derived mesenchymal stromal cells.

Cerium (Ce) is a promising candidate ion for application in bone tissue engineering (BTE) since it reduces the presence of reactive oxygen species. Ce-doped mesoporous bioactive glass nanoparticles (MBGNs) serving as vectors for the local application of Ce already demonstrated stimulating effects on the expression of pro-osteogenic genes in Saos-2 cells. So far, there is no evidence available about the effects of Ce-doped MBGNs on the viability, osteogenic differentiation and the formation of the osseous extracellular matrix (ECM) of primary human bone marrow-derived mesenchymal stromal cells (BMSCs). Therefore, in this study, the biocompatibility of the ionic dissolution products (IDPs) of MBGNs containing increasing concentrations of CeO2(0.05 MCe-MBGNs, composition in mol%: 86.6SiO2-12.1CaO-1.3CeO2; and 0.2 MCe-MBGNs, composition in mol%: 86.0SiO2-11.8CaO-2.2CeO2) and unmodified MBGNs (composition in mol%: 86SiO2-14CaO) was evaluated using human BMSCs. Eventually, the impact of the MBGNs' IDPs on the cellular osteogenic differentiation and their ability to build and mature a primitive osseous ECM was assessed. The Ce-doped MBGNs had a positive influence on the viability and stimulated the cellular osteogenic differentiation of human BMSCs evaluated by analyzing the activity of alkaline phosphate as a marker enzyme for osteoblasts in the present setting. Furthermore, the formation and calcification of a primitive osseous ECM was significantly stimulated in the presence of Ce-doped MBGNs in a positive concentration-dependent manner as demonstrated by an elevated presence of collagen and increased ECM calcification. The results of thisin-vitrostudy show that Ce-doped MBGNs are attractive candidates for further application in BTE.

Erratum to "Evaluation of MoPyC-prosthesis implantation and the use of angular stable plates in the treatment of comminuted radial head fractures" [J. Orthop. 16 (2019) 288-293].

[This corrects the article DOI: 10.1016/j.jor.2019.03.002.].

Prevalence of type 2 diabetes in Middle-East: Systematic review& meta-analysis.

BACKGROUND & OBJECTIVES: Type 2 diabetes is increasing in both developed and developing countries due to popularity of western lifestyle and population structure. Then, this systematic review aimed to identify the prevalence and trend of diabetes in the Middle-East region. METHOD: We searched Google Scholar, PubMed and Medline from 2000 up to 2018. MeSH terms were a combination of "diabetes", "prevalence", "diabetes mellitus", "type 2 diabetes", "Name of Countries" and "Middle East". Pooled estimates were obtained by means of random effect models to account for variation between studies. FINDING: Of the initially 669 identified articles, a total of 50 reports with 4,263,662 subjects met inclusion criteria. The combined prevalence of diabetes in the region was about 14.6% (95% CI: 11.6-17.5) which varied from 2.6% (95% CI: 2.5-2.6) to 21.9 (95% CI: 16.8-17.5) amongst countries. Therefore, approximately a total of 46 million individuals are now suffering from diabetes in the Middle East based on above-mentioned pooled estimate. CONCLUSION: The pattern and growing trend of diabetes during last 20 years in the study area is alarming and underline the point that maximal risk reduction for developing diabetes should be at the top of health priorities.

Superior biocompatibility and comparable osteoinductive properties: Sodium-reduced fluoride-containing bioactive glass belonging to the CaO-MgO-SiO2 system as a promising alternative to 45S5 bioactive glass.

Bioactive glasses (BGs) are promising bone substitute materials. However, under certain circumstances BGs such as the well-known 45S5 Bioglass® (composition in wt%: 45.0 SiO2, 24.5 Na2O, 24.5 CaO, 6.0 P2O5) act cytotoxic due to a strong increase in pH caused by a burst release of sodium ions. A potential alternative is a sodium-reduced fluoride-containing BG belonging to the CaO-MgO-SiO2 system, namely BG1d-BG (composition in wt%: 46.1 SiO2, 28.7 CaO, 8.8 MgO, 6.2 P2O5, 5.7 CaF2, 4.5 Na2O), that has already been evaluated in-vitro, in-vivo and in preliminary clinical trials. Before further application, however, BG1d-BG should be compared to the benchmark amongst BGs, the 45S5 Bioglass® composition, to classify its effect on cell viability, proliferation and osteogenic differentiation of human mesenchymal stem cells (MSCs). Therefore, in this study, the biocompatibility and osteogenic potential of both BGs were investigated in an indirect and direct culture setting to assess the effect of the ionic dissolution products and the BGs' physical presence on the cells. The results indicated an advantage of BG1d-BG over 45S5 Bioglass® regarding cell viability and proliferation. Both BGs induced an earlier onset of osteogenic differentiation and accelerated the expression of late osteoblast marker genes compared to the control group. In conclusion, BG1d-BG is an attractive candidate for further experimental investigation. The basic mechanisms behind the different impact on cell behavior should be assessed in further detail, e.g. by further alteration of the BG compositions.

Favorable angiogenic properties of the borosilicate bioactive glass 0106-B1 result in enhanced in vivo osteoid formation compared to 45S5 Bioglass.

The 45S5-bioactive glass (BG) composition is the most commonly investigated amongst BG-based bone substitutes. By changing BG compositions and by addition of therapeutically active ions such as boron, the biological features of BGs can be tailored towards specific needs and possible drawbacks can be overcome. The borosilicate glass 0106-B1 (composition in wt%: 37.5 SiO2, 22.6 CaO, 5.9 Na2O, 4.0 P2O5, 12.0 K2O, 5.5 MgO, 12.5 B2O3) has demonstrated pro-angiogenic properties. However, the osteogenic performance of the 0106-B1-BG and its influence on cell viability and proliferation in vitro as well as its osteogenic and angiogenic properties in vivo have not been investigated. Therefore, in this study, the impact of 0106-B1-BG and 45S5-BG on osteogenic differentiation, viability and proliferation on human mesenchymal stromal cells (MSCs) was assessed in vitro. Furthermore, MSC-seeded scaffolds made from both BG types were implanted subcutaneously in immunodeficient mice for 10 weeks. Osteoid formation was quantified by histomorphometry, vascularization was visualized by immunohistological staining. Additionally, the in vivo expression patterns of genes correlating with osteogenesis and angiogenesis were analyzed. In vitro, the impact of 45S5-BG and 0106-B1-BG on the proliferation, viability and osteogenic differentiation of MSCs was comparable. In vivo, scaffolds made from 0106-B1-BG significantly outperformed the 45S5-BG-based scaffolds regarding the amount and maturation of the osteoid. Furthermore, 0106-B1-BG-based scaffolds showed significantly increased angiogenic gene expression patterns. In conclusion, the beneficial angiogenic properties of 0106-B1-BG result in improved osteogenic properties in vivo, making the 0106-B1-BG a promising candidate for further investigation, e.g. in a bone defect model.

Use of Masquelet technique in treatment of septic and atrophic fracture nonunion.

BACKGROUND: Treatment of atrophic non-unions and large bone defects or infections remains a challenging task for the treating surgeon. In the herein study, we present our experience of the 'Masquelet technique' according to the 'diamond concept' for the treatment of complex long bone reconstruction procedures. METHODS: Between February 2010 and March 2015, 150 patients (mean age 51.4) with atrophic and- /or infected non-unions were included in this prospective study. All patients received autologous bone graft, a graft expander (TCP (tricalcium phosphate)) and BMP (bone morphogenic protein). Clinical and radiological parameters were assessed at 6 weeks, and at 3, 6 and 12 months. The SF-12 questionnaire was used to evaluate the subjective health of patients. RESULTS: A successful bony consolidation of the non-unions was observed in 120 (80%) cases with a median healing time of 12.1 months. The mean defect gap was 4.4cm. Initial infection was documented in 54 cases. The most frequently identified pathogen was staphylococcus epidermidis and staphylococcus aureus. A successful removal of microorganisms with subsequent healing was achieved in 39 cases (72%). The SF-12 scores of subjective physical and mental health increased from PCS 31.5 preoperatively to 36.7 one year postoperatively, while MCS increased from 45.5 to 48.7. CONCLUSIONS: Our study showed that the Masquelet technique according to the 'diamond concept' is a valid method to treat complex atrophic non-unions with large bone defects and associated infection. Following the principles of the 'diamond concept' (targeted optimization of tissue engineering and bone regeneration) a high rate of success can be expected in these difficult reconstruction cases.

Evaluation of MoPyC-prosthesis implantation and the use of angular stable plates in the treatment of comminuted radial head fractures.

OBJECTIVE: Comminuted radial head fractures are disproportionately often accompanied by injuries of the bone or ligaments and can be treated in different ways. METHODS: 15 patients with a comminuted radial head fracture were treated with an angular stable plate (=G1) and 8 with a MoPyC-prosthesis (=G2). RESULTS: G1 shows an average Morrey-score of 83,87 points. Complications occurred in 5/15 patients. Within G2 an average Morrey-score of 86 was achieved. Complications could be shown in 2/8 patients. CONCLUSION: Both the treatment provides a clear individual benefit for the patients and predict promising results for the treatment of comminuted radial head fractures.