A nested conical passive magnetic bearing is presented. The bearing consists of a nested conical rotor inside a conical stator, i.e. two coaxial tilted rings of permanent magnets, both with a rectangular cross section. Varying the cone or tilt angle of the rotor and stator we determine the rotor radius that provides the highest force for three different magnetization cases. For this optimal rotor radius, we show that the bearing with the highest volume normalized force also has the highest stiffness, and furthermore often also the highest varying stiffness with axial displacement. Finally, we show that a conical bearings with a tilt angle of  The high magnetisation allows for a strong repulsive force between sets of opposing magnets, thus supplying the lift for even heavy rotating parts.With an increasing focus on energy efficiency, there is a desire to identify and reduce any losses. For rotary machines such losses typically occur as friction at the bearings. Since the development of the strong rare earth based permanent magnets in the 1970’ies and 1980’ies11 levitation based on non-diamagnetic materials can never be stable in all directions, except in cases where the bearing utilizes a gyroscopic effect28. Thus, a magnetic bearing based on the repulsion between permanent magnets is inherently unstable. In order to function, some degree of stability is required in the lift  direction. This will result in instability in the radial direction and therefore some kind of stabilising, i.e. restoring, force is required in the radial direction. Such a stabilising bearing is referred to as an active magnetic bearing, while the permanent magnet assembly providing the lift is referred to as the passive bearing.However, as proven by the British mathematician Samuel Earnshaw in 184237. He found that the lifting strength was the same if the rings were radially magnetised. Similar results for the stiffness were later found semi-analytically by Ravaud etal.27 for solid rings of repulsive permanent magnets, and stacks of such systems have also been studied38. Closed form expressions for the lift has also been derived analytically21. Such systems have also been tested experimentally25.Initial modelling studies of the simplest type of passive magnetic bearing, namely two axially magnetised rings stacked on top of each other was done by Yonnet6. To validate the models experimental setups for testing bearings both concentric and off-centre have been presented39. The design with the maximum radial stiffness has been found numerically in Ref.22, by considering the air gap between rotor and stator. Optimally, a bearing configuration should provide both lift and stability, and thus concepts have been suggested with magnet placements attempting to achieve this24. The dynamics of the active bearing has also been investigated32.A large number of papers have been published on different passive bearing configurations. The stiffness and lift in different situations have been studied both numerically and experimentally, often with a comparison to models, see e.g. Ref.For all passive bearings, it is the stiffness of the radial component that determines the active force needed to keep the bearing stable. A lower negative value of this means a lower force and thus less required energy. However, in all existing studied bearings, the ideal balance between the provided lift and axial stability and the radial instability has not been reached. While bearings with low instability have been realized, the stiffness often varies with axial displacement, making it hard to realize an easily controllable active bearing.In the current study we analyse a parameterised system designed to supply both lift and stability, by a nested concentric placement of two conical rings. The idea is that if the bearing is shaped like two nested conical rings, with the rotor inside the stator, the magnetic forces will both have a component providing a lifting force along the axis of the bearing, but also a component along the radial direction, which might allow the stiffness along this direction to be designed as desired.1, but here the tilting of the concentric magnetic rings were not considered, i.e. the bearing was not truly cone-shaped. A number of cone-shaped active magnetic bearings have been considered20, including complex structures with cone-shaped teeth35 and bearing for use in magnetically suspended flywheels34. However, all of these works considers the dynamics of the active bearing and not the properties of a nested conical passive bearing.The properties of a conically nested passive magnetic bearing have not previously been considered in literature. The properties of a number of concentric bearings stacked in a cone-shape has been considered19.The bearing investigated here is a passive bearing and will thus always be unstable in one direction, as per Earnshaws theorem, ignoring dynamic effects. The bearing will thus have to be stabilized by an active magnetic bearing, as is always the case for a passive magnetic bearing29. The specific model used here has previously been used to calculate the force of passive magnetic bearings and compared with experiments with good agreement24. For these reasons, the results of the modeling work presented here are directly applicable to practical real-world passive magnetic bearings.Here the forces in the nested conical bearing are found through modelling using the finite element framework Comsol Multiphysics, which is applicable as the bearing is axi-symmetric. This means that the modelling can be performed at high resolution. A modeling approach is justified, as the bearing modelled is a fully magnetostatic system for which simulated magnetic fields are know to fully reproduce experimentally measured fields, see e.g. Refs.z-direction, 11, which states that the sum of the three stiffness components is equal to zero. Here we consider a bearing with a radial symmetry where thus z-direction asWe consider an axi-symmetric bearing which provides a force in the To determine the force and stiffness of the bearing considered, we have realized a magnetostatic finite element (FEM) axi-symmetric model of the bearing in Comsol Multiphysics. The equation solved in the FEM framework is the magnetic scalar potential equation11To determine the force on either the stator or the rotor, Maxwell’s stress tensor, As both the rotor and stator are axi-symmetric, there is no angular dependence on the force. This also means that the force on the rotor will be the same regardless of the rotation speed of the rotor.GMRES, which is a Generalized Minimum RESidual iterative method solver, is used to solve Eq. (6. As the system modelled is a magnetostatic system, the finite element modeling approach is known to fully reproduce the field created by experimental setups. Therefore a pure modeling is justified.The built-in Comsol Multiphysics solver olve Eq.  on the fz-axis. The stator has a magnetization direction that is along the inwards normal to its surface, while the rotor has an outwards magnetization direction normal to its surface. Thus, there is repulsion between the rings. Switching both magnetization directions results in an identical situation. It is noted that while producing such tilted conical rings of permanents magnets can be difficult if the rings are to be one piece, the rings can easily be made of cubes of permanent magnets placed in a ring, similar to Ref.24.We consider a bearing consisting of nested conical axi-symmetric magnet rings with a quadratic, i.e. square, cross-section. This bearing concept is illustrated in Fig. z-value at which the stator and rotor have a minimum distance between them of 0.2 mm as shown in Fig. 38.In order to ensure that there is always a clearance between the rotor and the stator, we define the value of entclass1pt{minimaentclass1pt{minima17. The three different magnetization directions considered are the single bearing, which consists of two tilted concentric rings with opposite magnetization, the double bearing which is similar to the single bearing, except with two magnets in each tilted ring, and finally the alternating bearing is similar to the double bearing, except that the magnetization of one part of the magnet is reversed in both the stator and rotor rings. We assume that the permanent magnets in the bearing have a remanence of 1.4 T and a relative permeability of 15.We also consider extended ring geometries, with twice the cross-section and different magnetization directions, as shown in Fig. 3.All results presented in this manuscript are directly available from the data repository in Ref.Initially, a variation study was conducted to determine the optimal geometry of a bearing as function of the tilt angle and the bearing type. Tilt angles from z-position, For each of these 21 bearings the radius of the rotor, z-direction normalized with respect to the total volume of the magnet rings in both the stator and the rotor.When the rotor radius is varied the volume of it changes. To account for this, in the following we consider the force in the An adaptive routine is used to determine the optimal rotor radius to a precision of 0.1 mm. First, the volume normalized force was computed in steps of 0.5 mm for z, i.e. calculate values different from For all bearings the value of For each for the optimal Notice that for high z. This was done to smooth out small numerical variations in the force calculations, which can lead to large variations in the computed stiffness. The volume normalized stiffness in the For each volume normalized force curve, we fitted a double exponential function of the form entclass1pt{minimaWe can also directly compare the force provided by the bearing and the axial stiffness of the bearing. Shown in Fig. Typically the desired properties of a bearing are that it provides a high amount of lift at a relative low absolute stiffness, such that the required force from the active bearing is as small as possible. Of course a relative low stiffness will mean a high displacement with varying load, so the choice of stiffness is always a compromise. An initial idea to improve the performance of the bearing is to scale it up. As the magnetic field scales with the geometry of the bearing, the absolute lift of the bearing will increase as the size of the bearing is increased. However, the relative stiffness, which is the gradient of the force with respect to the size of the bearing remains constant.z-range considered here. This would be a bearing that has a constant z-range considered, but which also provides a high force over this range. This can be investigated by considering the relative standard deviation, z-range considered. This is shown in Fig. z-range considered, i.e. which are stable in the z-direction. It is noted that This argument shows that scaling the bearing can be used to provide more lift, but it does not change the stiffness of the bearing. Therefore it is crucial to consider more in-depth the stability of the bearings simulated here. Considering this, we determine the bearing which would be easiest to control by an active bearing over the Choosing the best bearing from Fig. z, with a large force at When a smaller 37. Indeed, the It is noted that the 24.Additional methods to improve the force and stiffness of the presented bearings may also be considered. One option is to consider the shape and also exact magnetization direction of the two opposing rings in the single configuration. Only the doubling in one direction has been studied here, but other changes could be considered. Varying the exact direction of the magnetization in the rings could also be explored, to see if better configurations could be determined. Another option could be to look at closing the flux loop on the “back” side of both the rotor and stator rings in the alternating design with iron pieces. Previously, this has been shown to increase the stiffness and lift in a magnetic bearingFinally, we remark that the conical bearing could also be reversed, such that the bearing provided an attractive force. In this configuration it could be used in an “upside-down” configuration to compensate gravity on the rotor by supplying a pull instead of a lift.We presented a concentric magnetic bearing consisting of two coaxial nested concentric rings of opposing permanent magnets as the rotor and stator. Both magnet rings had a rectangular cross-section. We examined three different configurations, and determined the rotor radius that provided the highest force as a function of the tilt angles of the stator and rotor rings.z, a bearing with a tilt angle of For this optimal rotor radius, we showed that the bearing with the highest force also has the highest stiffness, and furthermore often also the highest variation in stiffness with axial displacement. Over a 1 mm displacement in


Pathophysiology (ISSN 1873-149X), the flagship journal of the International Society for Pathophysiology (ISP) [Pathophysiology. Our editorial and publishing teams appreciate the help of Elsevier publishing in making this a very smooth transition. We would also like to thank Dr. Olga Pechanova, the current president of the ISP, for her significant efforts in securing these transfer processes.The recent transfer of ogy ISSN 873-149X,gy (ISP)  to MDPI Pathophysiology remains an international, “open access” and peer-reviewed journal that provides a progressive platform for publishing studies related to the mechanistic basis, disease characteristics and therapies for diverse diseases. The emphasis of our journal’s title Pathophysiology is inherently extensive as a “discipline” and anticipates that published reports will include diagnostic, prognostic and mechanistic studies on disease, including novel therapeutic approaches and therapeutics.Our journal was initially inaugurated by Prof. Toshikazu Yoshikawa of the Kyoto Prefectural University of Medicine, Department of Molecular Gastroenterology and Hepatology, in 1994 as a quarterly journal with Elsevier with the participation of Dr. D. Neil Granger, Dr. Osmo Hänninen and Dr. Osamu Matsuo as regional editors. With MDPI, we hope to continue this legacy of research, scholarship and communication. As such, Pathophysiology cannot be overemphasized. As we take these first steps to redefine the scope of our journal with an emphasis on rapidly publicizing the newest and most highly important works in this field, we will seek to maintain a high level of familiarity in terms of editorial sophistication to allow such expedited reviewing. Therefore, we have now expanded the range of the disciplines of our editorial board members working in science and medicine, and have empanelled a large and extensive board of specialists drawn from many different disciplines to participate in reviewing submitted content. Consequently, we now draw on a large pool of active physiologists, neurologists, immunologists and pathologists with many cumulative decades of experience at the bench and in peer-reviewing and publishing such work to provide rapid responses to bring the best work out very rapidly.Our now (hopefully) post-COVID era is a critical historical breakwater. We are entering a period with many new challenges in terms of disease detection as well as population-based and personalized/precision medical treatments where the weight of Pathophysiology.The ISP also represents a worldwide network of scientists, many of whom are in Europe and are interested in creating inter-institutional and cross-disciplinary collaborations. As resources for science become increasingly more precious, we hope that participation in the ISP and submission to our journal become a regular endeavor. We invite all interested basic and clinical scientists to submit their best and boldest reports to


N-formyl imidazole obtained by the reaction of 1,1′-carbonyldiimidazole and formic acid in dimethyl sulfoxide as a solvent. Starch formates are soluble in polar aprotic solvents, not susceptible against hydrolysis, and not meltable. Thermoplastics could be generated by conversion of starch formates with long-chain fatty acids exemplified by the conversion with lauroyl chloride in N,N-dimethylacetamide, leading to mixed starch laurate formates. The mixed esters show melting temperatures mainly dependent on the amount of laurate ester moieties.Starch can be efficiently converted into the corresponding formates homogeneously using  Polysaccharide esters play an important role in various fields of application, e.g., as foils, films, filters, and thermoplastic to replace plastics based on fossil resources. Thermoplastic starch may be obtained by derivatisation with long-chain fatty acids that yields a disturbance of the intra- and intermolecular hydrogen bonds of the polysaccharide ,2,3. WhiN-formyl imidazole : C = 43.63, H = 4.28, N = 0.59.1H NMR  [ppm]: δ = 8.23 (-CHO), 5.5–3.5 (AGU).13C NMR  [ppm]: δ = 162–160 (C 7), 97.04 (C 1′), 75.53 (C 4), 72.20 (C 3s), 70.14 (C 2s), 69.02 (C 5), 61.96 (C 6s).2a  in 25 mL DMAc, lauroyl chloride  was added and the mixture was allowed to react for 3 h at 80 °C under stirring. After cooling to room temperature, the mixture was poured into 250 mL methanol. The precipitated formed was filtered off, washed four times with 100 mL methanol each, and was dried in vacuum at 40 °C.To a solution of starch formate 3aProduct: Yield: 2.08 g .formate: 0.48, DSlaurate: 2.51.DS1H NMR  [ppm]: δ = 8.10 (CHO), 5.75–3.50 (AGU), 2.35 (H 8), 1.51 (H 9), 1.25 (H 10–H 17), 0.87 (H 18).13C NMR  [ppm]: δ = 173.37 (C 7laurate), 160.65 (CHO), 95.93 (C 1′), 72.20–68.98 , 62.31 (C 6s), 34.09 (C 8), 32.08 (C 16), 29.54 (C 10–C 15), 24.97 (C 9), 22.81 (C 17), 14.23 (C 18).N-formyl imidazole obtained by the reaction of formic acid with 1,1′-carbonyldiimidazole was developed yielding highly substituted products with DS of up to 2.55. The starch formates are soluble in polar aprotic solvents, unexpectedly stable against hdrolysis, and do not melt. However, the conversion of the starch formates by subsequent reaction with lauric acid chloride, e.g., yields mixed starch esters that are thermoplastic and melt at low temperature of 125 °C to 185 °C, depending on the DS values. The thermoplastic properties of these novel materials are under investigation.An efficient process for the preparation of pure starch formates by conversion of starch with Formate groups could act as protecting groups for the hydroxyl groups. Moreover, starch formate may act as a polymer-bound CO surrogate or CO-releasing molecule for application in organic synthesis  or in m


Parallel stent-stent grafting is a major endovascular technique used to preserve the supra-aortic branches during thoracic endovascular aortic repair (TEVAR) of aortic pathologies involving the aortic arch. The short- and mid-term results of this technique are satisfactory; however, endoleak remains a major concern. Thus, here we designed a new chimney stent-graft to decrease the endoleak rate.To testify the feasibility and safety of the new chimney stent-graft system in a canine model.Six Labrador retrievers were used. Pre-operative data were collected and all operations were performed under general anesthesia. The main and chimney stent-grafts were implanted through the abdominal aorta and left subclavian artery approaches, respectively. Completion digital subtraction angiography (DSA) was performed to confirm the immediate outcomes. All dogs were fed separately for 6 months and sacrificed after aortic angiography. The thoracic aorta and the main and chimney stent-grafts were harvested for histopathologic examination.No complications were found in follow-up DSA. All branch arteries were patent. Inflammatory responses were observed around the stent-grafts in 3 experimental animals, and slight hyperplasia was observed in the surrounding tissues compared with the normal vessels. There was no mural thrombus in the stent, endothelial cells were noted on the inner surface of the stent, and thrombus was formed in the outer skirt and gutter area. The histopathologic examinations revealed similar results to those of gross necropsy observations.This study demonstrated the feasibility and safety of the Longuette stent-graft and the first to report a revised stent-graft specific for chimney technique. Chimney and fenestration/branch techniques are the most commonly used endovascular techniques to preserve the supra-arch branches in thoracic endovascular aortic repair (TEVAR). Although satisfactory results were reported in various centers, endoleak remains a major concern. Type I endoleak occurs in 7–23.1% of cases treated using the chimney technique, mostly from the gutter between the chimney and aortic stents.The study was approved by the ethics committee of the Second Xiangya Hospital.The self-expanding stent-graft is composed of a Ni-Ti metal scaffold and an expanded polytetrafluoroethylene graft woven to the surface of the scaffold with a “skirt-shaped” structure. After its release, the outer stent-graft fills the gutter area outside the inner main chimney stent aiming to decrease the incidence of endoleak. Additionally, the inner main stent is designed with greater radial force than the outer stent to ensure its patency . The steThe surgical experiment was performed in 6 Labrador retrievers at the Advanced Animal Study Services Center, Shenzhen, China, to test the safety and feasibility of the device system. The animals were provided by Jiagan Biotech Co. Ltd., Shanghai, China. The mean pre-operative weight was 29.1 ± 1.85 kg. The pre-operative profiles of the animals are listed in The anatomic data were acquired by pre-operative digital subtraction angiography (DSA) in all animals 7 days prior to surgery. The aortic and chimney stent-grafts were prepared based on the DSA measurements. All the procedures were performed under general anesthesia.After intramuscular premedication with zolezapam (5 mg/kg body weight [BW]), intravenous anesthesia was induced by propofol (8 mg/kg BW) and maintained by the continuous inhalation of isoflurane. The dogs were endotracheally intubated and ventilated at 200 mL at 10–16 breaths per minute using 30% oxygen. Heparin (300 IU/kg BW) was given intravenously for anticoagulation. A mid-abdominal incision was made and the abdominal aorta was carefully dissected. A 6F sheath was introduced into the abdominal aorta. Another incision was made in the left neck and the left subclavian artery (LSA) was dissected. A 5F sheath was introduced into the LSA. The pigtail catheter was advanced into the ascending aorta over a 0.035” guidewire. Then the guidewire was removed, and angiography was performed via the pigtail catheter. The diameters of the aortic arch and the LSA were remeasured for final confirmation of the stent-graft choices. Lunderquist guidewires were then advanced to the ascending aorta via the abdominal and LSA access points, respectively. Both sheaths were removed and delivery systems of both stent-grafts were advanced through the abdominal aorta and the LSA access points, respectively. The aorta stent-graft was first deployed at the aortic arch distal to the orifice of the innominate artery with total coverage of the LSA. After the deployment of the aorta stent-graft, the chimney stent-graft was half released until the outer layer was fully expanded. The entire delivery system was then carefully retracted until the outer layer was close and proximal to the orifice of the LSA . CompletAfter recovering from anesthesia, the dogs were fed separately and continuously observed for appetite, movement, and mental state. Dual antiplatelet therapy consisting of clopidogrel 75 mg and aspirin 100 mg per day was given to all dogs to prevent thrombosis. Cefotaxime sodium was administered for 3 consecutive days postoperatively in all dogs. All dogs underwent a second aortic angiography to exclude adverse events and were sacrificed 6 months after stent-graft implantation by the intravenous injection of 10% potassium chloride. The entire thoracic aorta and stent-grafts were acquired for gross pathology and histological evaluations.Stent-graft deployment was successful in all six dogs. No major bleeding or cardiac events occurred throughout the preparation and implantation periods. No retrograde type A dissections occurred during implantation.The anatomic data were acquired by pre-operative DSA. The anatomic features and stent-graft types are listed in The mean procedure time was 149 ± 16.6 min. The abdominal aorta and LSA were exposed safely without complications. The mean procedure time for exposure was 20 ± 2.94 min. Stent-graft delivery and deployment occurred precisely without accident. On the completion DSA, the stent-graft positions were confirmed to be fixed without migration. All branch arteries were patent .Fig. 3ExPostoperative appetite, mobility, and mental status were normal in all dogs. Mean post-operative weight was 29.3 ± 1.95 kg. No complications were found prior to sacrifice. After follow-up DSA was performed at 6 months, all dogs were sacrificed under general anesthesia and the thoracic aorta was harvested and embedded in paraffin for further histological staining and analysis .Fig. 4ThNo complications were found on the follow-up DSA. All branch arteries were patent . No dissThe histopathologic exams showed similar results to those of the gross necropsy observations. Slight inflammation was observed in the vessels at the implantation site. A small number of inflammatory cells were visible in the tissue surrounding the scaffold and the coated material, but no mural thrombi were noted in the main and chimney stent-grafts .Fig. 6HiThe main technical problem with the chimney technique is the risk of type Ia endoleak through the gutters between the main aortic and the parallel graft.,Although there is insufficient evidence regarding the performance of bare and covered stents as chimney stents, some experts believe that the risk of perfusion into the gutters and retrograde flow from the aortic arch is greater with bare than covered stents.The possibility of the “outer skirt” unintentionally covering the adjacent branch artery may be worrisome. In this experimental study, no such complications were found. The “outer skirt” is 6–10 mm larger than the main graft; depending on the diameter, it is unlikely to cover the adjacent artery. Moreover, the Longuette stent-graft can be deployed more proximally into the aorta cavity if the orifices of the branch arteries are very close together.Finally, the experimental study has limitations. Besides the limited number of animals and short observation time, further studies should be performed in pathological models like aneurysm or dissection. The possible interference between multiple Longuette stent-grafts should also be tested.The Longuette stent-graft is the first reported revised stent-graft specific for chimney technique. This experimental study proved the feasibility and safety of this stent-graft. These results suggest that the use of this graft might improve clinical outcomes after chimney TEVAR.The authors declare that they have no conflicts of interests to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.


The goal of this review is to provide further understanding of increased vascular stiffness with aging, and how it contributes to the adverse effects of major human diseases. Differences in stiffness down the aortic tree are discussed, a topic requiring further research, because most prior work only examined one location in the aorta. It is also important to understand the divergent effects of increased aortic stiffness between males and females, principally due to the protective role of female sex hormones prior to menopause. Another goal is to review human and non-human primate data and contrast them with data in rodents. This is particularly important for understanding sex differences in vascular stiffness with aging as well as the changes in vascular stiffness before and after menopause in females, as this is controversial. This area of research necessitates studies in humans and non-human primates, since rodents do not go through menopause. The most important mechanism studied as a cause of age-related increases in vascular stiffness is an alteration in the vascular extracellular matrix resulting from an increase in collagen and decrease in elastin. However, there are other mechanisms mediating increased vascular stiffness, such as collagen and elastin disarray, calcium deposition, endothelial dysfunction, and the number of vascular smooth muscle cells (VSMCs). Populations with increased longevity, who live in areas called “Blue Zones,” are also discussed as they provide additional insights into mechanisms that protect against age-related increases in vascular stiffness. Such increases in vascular stiffness are important in mediating the adverse effects of major cardiovascular diseases, including atherosclerosis, hypertension and diabetes, but require further research into their mechanisms and treatment. The goal of this article is to review what is known about changes in vascular stiffness with aging and disease. It is widely accepted that aortic stiffness increases with advancing age. However, most existing research employs measures of aortic stiffness at a single aortic location as an estimate of overall aortic stiffness. This makes it a challenge to understand age-related stiffness along the length of the aortic tree, from the aortic root to its bifurcation into the iliac arteries, and regional vessels. Another goal is to review human and non-human primate data, which is particularly important for understanding sex differences in vascular stiffness with aging and the changes in vascular stiffness before and after menopause in females. Several mechanisms that mediate the increases in vascular stiffness will be reviewed. The most well-studied mechanism involves the extracellular matrix, with increases in vascular collagen and decreases in vascular elastin. There are other mechanisms, less well studied, that also contribute to the increased vascular stiffness, e.g., collagen and elastin disarray and increased vascular smooth muscle cell stiffness and numbers. Further insight can also be gained from populations with an extended lifespan, living in areas called “Blue Zones,” where a healthy diet and exercise ameliorate the increases in vascular stiffness observed with age.The aorta is divided into sections by location; the ascending aorta, aortic arch, and the descending aorta. The descending aorta can be divided into thoracic and abdominal sections. Branches of interest include the left and right coronary arteries, which branch from the aortic root, and the brachiocephalic, left carotid, and left subclavian, which branch from the aortic arch. As the aorta descends there are numerous branches which supply the surrounding muscles and organs including intercostal, celiac, hepatic, gastric, splenic, renal, mesenteric, and gonadal arteries. The abdominal aorta bifurcates into the iliac arteries which extend inferiorly, turning into the femoral arteries, which supply blood flow to each leg.The morphometric properties of the aorta differ along its length. The aorta tapers, with the average systolic diameter decreasing from the proximal to the distal aortic tree . In healin vivo , is an estimate of the pulse transit-time between the carotid and femoral arteries . This isin vivo . In humain vivo . Anotherin vivo . Variatiranching . Isolateth aging .in vivo studies reported that increases in thoracic aortic stiffness with aging were greater than, or similar to those observed in the abdominal aorta , resulting from an increase in collagen and decrease in elastin. The ECM is composed of a complex network of different matrix proteins, metalloproteases, and glycosaminoglycans, which are also responsible for the structural integrity of the vasculature, and therefore contribute to its stiffness . CollageUnlike collagen, elastin, the other major ECM protein, provides flexibility and extensibility of the vessel wall . Elastinin vivo  release . ReducedAge-related endothelial dysfunction may affect the arterial network differently based on location and vessel type. Aging results in endothelial dysfunction in the aorta but not in the femoral artery . The anaVascular smooth muscle cells have recently been discovered as important contributors to age-related increases in arterial stiffness . This meAs emphasized in this review, increased aortic stiffness is mainly associated with aging. Interestingly, children with Hutchinson-Gilford progeria syndrome, a premature aging syndrome with a mean lifespan of 13 years, experience severe arterial stiffening from a young age. Patients aged 7 years have the aortic stiffness of a 60–69-year old without additional diseases . This isStudying populations and animal models that experience longevity without cardiovascular decline and consequent increases in vascular stiffness could provide new insights into delaying vascular aging and promoting vascular health. Populations with extended lifespan live in areas known as Blue Zones . They arObesity, one of the most common worldwide problems, is associated with almost all cardiovascular diseases, including increased vascular stiffness . ConversHowever, vascular stiffness has not been evaluated in most studies of animal models with an extended lifespan. Whales, for example, are some of the longest living mammals but not much is known about the aging of their vasculature. They have a vastly different structure to their aortic tree with an anatomy representing arterial adaptation by diving mammals . Of inteAn exception to this is the naked mole-rat, which is the longest-lived rodent known . This roAging-related vascular stiffening is sexually dimorphic, a topic that has not been studied extensively. Although arterial stiffness increases from young adulthood to older ages in both men and women, the increases in stiffness in women before menopause are less than those in age-matched men . This paMuch of the previous experimental work on vascular stiffness has been performed in rodent models, which have a short lifespan and do not experience menopause. Because of this, the most relevant studies are those in non-human primates and humans. Non-human primates have a longer lifespan (>30 years), and undergo menopause like humans but are exempt from diseases, such as atherosclerosis, hypertension and diabetes, which are confounding factors when studying age-related changes in vascular stiffness in humans .The studies considered here, on sex differences in arterial stiffness in humans, will focus predominantly on primary measures of arterial stiffness, namely, PWV, pulse pressure, and aortic distensibility; PWV and pulse pressure increasing and aortic distensibility decreasing as age and stiffness increases. In a study involving 777 people aged 21–85 years, aortic distensibility and aortic PWV were assessed using cardiovascular MRI, with age-related differences examined in successive deciles in each sex . In the It is important to note that, although aortic stiffness is more severe in males than females prior to menopause, pre-menopausal women also exhibit age-dependent increases in aortic stiffness, as observed in primates . An aortThe mechanisms underlying age-related and regional differences in aortic stiffness are also sexually dimorphic. In non-human primate models, aging-related changes in gene expression have been shown to be sex-dependent and to involve key contributors of vascular stiffness, such as ECM composition, VSMC phenotype, cell signaling pathways, resistance to apoptosis, metabolism, protein synthesis, and transcription factors. Aging male, but not female monkeys, show downregulation of collagen type III protein expression and upregulation of collagen type VIII transcript levels. Collagen type III decreases collagen bundle size and increases vascular elasticity while collagen type VIII promotes VSMC migration into the intima . This maThe greater increases in vascular stiffness in aged-matched men, than in women prior to menopause, is reversed, so that after menopause women show more severe increases in vascular stiffness. The difference in vascular stiffness between pre- and postmenopausal women is primarily ascribed to proposed protective roles of estrogen, which reduces increased stiffness with age. Estrogen levels rapidly decrease just before menopause and continue to fall after menopause . This coIn mice, NO bioavailability has been directly linked to the mechanical properties of the vessel wall, corroborating that the effect of estrogen is mediated by NO. Female ovariectomized mice display increased circumferential elastic modulus in all arteries, suggesting stiffening, as well as decreased eNOS protein expression, and reduced endogenous NO production . Female 4 (tetrahydrobiopterin), a critical cofactor for NO production, increased carotid artery compliance and brachial artery flow-mediated dilatation in postmenopausal, but not premenopausal women . However, after adjustment in the data of outliers, the association remained significant only in men , and have stiffer aortae than controls. The ratio of CD31+/CD42– microparticles to EPCs was found to be directly associated with arterial PWV (aPWV)  . This suV (aPWV) . In addiV (aPWV) .Elevated oxidative stress also plays a role in increased arterial stiffening in patients with atherosclerosis. A study examining patients with peripheral arterial disease found an independent association of aPWV with serum levels of osteopontin and oxidized low-density lipoprotein, which are involved in oxidative stress, thus supporting the role for oxidative stress in mediating arterial stiffness in patients with atherosclerosis .Intimal arterial calcification within atherosclerotic plaques may also be responsible for increased vascular stiffness . A studyper se  are associated with decreased total systemic arterial compliance and increased aortic augmentation index, indicating increased central artery stiffness . CentralAs noted throughout this review, an important mechanism mediating increased vascular stiffness is increased oxidative stress . It is wEven patients with prediabetes experience increased arterial stiffness. In one study, diabetes was associated with higher aortic PWV and prediabetes was associated with higher brachial-ankle PWV, a measure of composite stiffness . SimilarOne of the most important effects of aging on the cardiovascular system is a progressive increase in vascular stiffness. Understanding the extent to which vascular stiffness increases with aging and the mechanisms involved are important, since vascular stiffness is a critical factor in mediating the adverse effects of most cardiovascular diseases, including atherosclerosis, hypertension and diabetes. Many prior studies are limited in defining changes in vascular stiffness down the aortic tree, because only one section of the aorta was studied. We found that abdominal aortic stiffness is greater than thoracic aortic stiffness. However, this topic warrants further investigation as there are major sex differences. In men vascular stiffness increases progressively from young adulthood to old age. In women vascular stiffness increases, but to a lesser extent up to menopause, and then increases at a rate exceeding that for males after menopause. Less data are available on sex differences in animals, since the most commonly studied species are rodents, where females do not go through menopause, Their relevance for understanding human disease, therefore, is limited. Studies of sex differences in the changes in vascular stiffness associated with age are best carried out in humans without associated cardiovascular diseases, and in non-human primates that live over 30 years and, like human females, go through menopause. Several mechanisms mediate the protection in females, with the most significant one being the female hormone, estrogen, which is present up to menopause and then declines. Other important mechanisms of increased vascular stiffness include changes in the extracellular matrix, with increases in vascular collagen and decreases in vascular elastin. It is also known that calcium deposition and endothelial dysfunction in the vessels contribute to increased vascular stiffness. Less well studied mechanisms may also contribute, such as collagen and elastin disarray, and increased vascular smooth muscle cell stiffness and numbers. Additional insights come from studies in populations with an extended lifespan that live in areas known as “Blue Zones.” People in these areas maintain a healthy diet and daily exercise and have lesser increases in vascular stiffness with age. Understanding how these environmental factors influence the progression of vascular stiffness may provide critical insights into retarding its progression and, thereby reducing cardiovascular disease.As elucidated in this review, considerable progress has been made in understanding the role of vascular stiffness in normal biology and aging as well as in mediating changes in disease states. However, considerably more work needs to be done in this field. Differences in stiffness down the aortic tree in regional arteries and veins and arterial resistance vessels requires further research, since most prior work only examined the aorta. More work is also required to understand the divergent effects of increased aortic stiffness in males and females, and the role of sex hormones in mediating those differences. There is much more to be learned about the molecular mechanisms mediating changes in arterial stiffness. There is also much more clarification needed to understand the relationship between disease states in affecting changes in vascular stiffness, and conversely, how vascular stiffness mediates disease states. An important example is atherosclerosis, where it is needed to understand the extent to which changes in vascular function in atherosclerosis are due to changes in vascular stiffness vs. changes due to atheroma.SV: conceptualization. SV, JZ, CV, KM, and DV: writing—original draft. SV, JZ, CV, KM, RG, and DV: writing—review and editing. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Nonunion following treatment of supracondylar femur fractures with lateral locked plates (LLP) has been reported to be as high as 21 %. Implant related and surgeon-controlled variables have been postulated to contribute to nonunion by modulating fracture-fixation construct stiffness. The purpose of this study is to evaluate the effect of surgeon-controlled factors on stiffness when treating supracondylar femur fractures with LLPs:Does plate length affect construct stiffness given the same plate material, fracture working length and type of screws?Does screw type  and number of screws affect construct stiffness given the same material, fracture working length, and plate length?Does fracture working length affect construct stiffness given the same plate material, length and type of screws?Does plate material (titanium versus stainless steel) affect construct stiffness given the same fracture working length, plate length, type and number of screws?Mechanical study of simulated supracondylar femur fractures treated with LLPs of varying lengths, screw types, fractureworking lenghts, and plate/screw material. Overall construct stiffness was evaluated using an Instron hydraulic testing apparatus.p = 0.003). The use of bicortical nonlocking screws decreased overall construct stiffness by 18 % compared to bicortical locking screws . The type of screw  and the number of screws in the diaphysis (3 vs. 10) did not appear to significantly influence construct stiffness . Similarly, fracture working length , and implant type  did also not appear to effect stiffness.Stiffness was 15 % higher comparing 13-hole to the 5-hole plates  reduced overall construct stiffness. Using more screws, using unicortical locking screws, increasing fracture working length and varying plate material (titanium vs. stainless steel) does not appear to significantly alter construct stiffness. Surgeons can adjust plate length and screw types to affect overall fracture-fixation construct stiffness; however, the optimal stiffness to promote healing remains unknown. Distal femur fractures are a common orthopaedic problem with an overall incidence of approximately 37 per 100,000 person-years . With thVarious implant related factors have been postulated to contribute to nonunion, presumably through the effect of modulating the overall construct stiffness. Among these, implant material (stainless steel vs. titanium), plate length, screw type, and screw density have received particular scrutiny , 24. TheThe purpose of this study is to evaluate the effect of surgeon-controlled factors on overall fracture-fixation construct stiffness when applying lateral locked plates in the treatment of supracondylar femur fractures:Does plate length affect construct stiffness given the same plate material, fracture working length and type of screws?Does screw type  and number of screws affect construct stiffness given the same material, fracture working length, and plate length?Does fracture working length affect construct stiffness given the same plate material, length and type of screws?Does plate material (titanium versus stainless steel) affect construct stiffness given the same fracture working length, plate length, type and number of screws?We performed a mechanical study on simulated supracondylar femur fractures using biomechanical femur models to evaluate the effect of surgeon-controlled variables on implant stiffness in 6 conditions.In order to examine the effect of plate length, screw types, number of screws, fracture working length and plate material 7 different configurations were tested Fig. . The “stLarge size 4th Generation Biomechanical Sawbone Femur Models were used , as our goal was to assess relative changes in construct stiffness in a consistent manner. These composite analougues femurs simulate structural properties and geometries of human bone, with a unique short fiber epoxy shell that mimic cortical bone which is filled with polyurethane foam resembling the bone marrow and cancellous bone at the epiphysis –27. All The distal femur constructs were tested for overall construct stiffness  in the axial direction. The proximal ends of the femurs were potted in a polyurethane elastomer and were placed in a custom-made jig with a shear relief apparatus in the vertical position. Axial compression from the distal end was applied to the constructs on an Instron hydraulic testing apparatus  Fig. . Each cop < 0.05 were considered statistically significant.Prior to the initiation of the study, we tested 5 intact and then instrumented models to determine stiffness values and to calibrate the testing jig. Based on this pilot study, five specimens per group were considered adequate to detect a 20 % change in the stiffness with 80 % power . A repeated measure analysis of variance (ANOVA) with stiffness as the dependent variable, group as fixed factor, while accounting for multiple measures from the same specimen (each test conducted in triplicate), was conducted using SPSS v23 . Two-tailed values of p = 0.003)     and number of screws affect construct stiffness given the same material, fracture working length, and plate length? The use of bicortical nonlocking screws decreased overall construct stiffness by 18 % compared to bicortical locking screws  Fig. b. The us76) Fig. c. Increap = 0.24)  was similar to those with long working length of 9.4 cm   affect construct stiffness given the same fracture working length, plate length, type and number of screws? The use of stainless steel as opposed to titanium for plate material did not appear to influence overall stiffness. The stiffness of constructs with stainless steel plates 904 N/mm) was similar to those with titanium plates  was evaluated, and other types of distal femur fractures and fixations were not assessed. In addition, the hybrid construct as a variation of utilizing locking and nonlocking screws was not evaluated. The model in this study primarily determines the stiffness of each osteosynthesis construct in its respective configuration under axial load; torsional and bending loads were not assessed in the current study. Another potential limitation is that results of this study are limited to the time zero of each construct, however as with any cadaveric or sawbone biomechanical study, there is an inherent time zero limitation, and these result does not investigate biologic factors such as biologic healing and muscle forces. In addition, cyclic loading was not implemented, which would have simulated the physiological scenario better. The synthetic bone itself most likely has very little effect on the construct stiffness, providing consistency between groups and allowing for better comparisons than would be possible with cadaveric specimens. However, as many of these injuries occur in the elderly, the magnitude of the effect of the changes on stiffness seen may be different in osteoporotic bones. Care should be taken in extrapolating the results to patients with poor bone quality, since some of the configurations in this study may result in early implant failure or cut out or cut through, in particular with bones with reduced quality. Finally, this study focused only on construct stiffness. Changes in plate length, screw type and number, and plate and screw material may also affect fatigue failure and load to catastrophic failure.We found that longer plates created a stiffer construct when plate material, screw type and number, and fracture working length were kept constant. Ricci et al. have shown that short plate length is a risk factor for nonunion . It may We found that the use of bicortical nonlocking screws is associated with a decrease in overall construct stiffness. This gives credence to the argument that nonlocking screws can be employed in the diaphysis, should quality of the bone stock allow it. This technique may be beneficial for allowing callus formation and indirect bone healing. There was no significant difference in stiffness comparing the use of bicortical and unicortical locking screws. This result is similar to the result of a study by Beingessner et al. that showed no effect on overall stiffness when comparing unicortical and bicortical locking screws in a similar construct . HoweverWe didn’t find filling all of the holes of the plate to have an effect on axial stiffness. This was in accordance with previous research showing that all locked, all unlocked, proximal unlocked, and distally unlocked plating construct did not differ in axial stiffness . This fip = 0.24)). In clinical practice, fractures have longer fracture line that can lead to a higher working length than tested for this study. In a retrospective review by W.H. Harvin et al., no significant difference in fracture union between shorter and higher working lengths was demonstrated. [Surprisingly, increasing the fracture working length did not have an effect of stiffness. With a working length of 5.4 cm, the stiffness was 995 N/mm, while increasing the working length to 9.4 cm decreased the stiffness to only 938 N/mm,  did not appear to influence overall construct stiffness. This finding contradicts the findings of two previous studies that showed stainless steel had greater stiffness in comparison with titanium , 46. HowMany supracondylar fractures have large areas of comminution, requiring a large gap between the distal most diaphyseal screw and the distal screw cluster. In our previous experience with supracondylar femur fractures treated with LLP, titanium plates have had a lower risk of nonuion . It may Surgeons can control a number of variable to influence the overall construct stiffness during lateral plating of supracondular femur fractures. Using shorter plates and using bicortical nonlocking screws  reduces overall construct stiffness. However, using more screws, using unicortical locking screws, increasing fracture working length and varying plate material (titanium vs. stainless steel) does not appear to significantly alter construct stiffness. Our data suggest when additional screws are needed, they may be placed without increasing stiffness. However, this observation should be verified in cadaveric and clinical studies. While surgeons can adjust plate length and screw types to affect overall fracture-fixation construct stiffness the optimal stiffness to promote healing remains unknown.


Background and aimThe diameter of the graft used for the reconstruction of the anterior cruciate ligament (ACL) is an important determinant for the overall strength and future outcome of the operative procedure. Preoperative prediction of quadrupled hamstrings autograft (QHAG) diameter can prove to be of help in forecasting the need for augmentation or alternative grafts like quadriceps, bone-patellar tendon-bone autograft, and synthetic grafts. The relationship between the preoperatively assessed anthropometric parameters and the obtained quadrupled hamstrings graft diameter has not been extensively studied, especially in the population of Indian origin. This study aimed at investigating whether a correlation exists between the measured anthropometric parameters like age, weight, height, thigh circumference, and body mass index (BMI) and the intraoperatively obtained diameter of hamstring graft for ACL reconstruction in the study population of Indian male subjects.Study designA prospective cohort study conducted in a tertiary care center and teaching hospital in a district in central Uttar Pradesh, India.MethodsThe preoperative anthropometric data  of 73 Indian male subjects undergoing primary ACL reconstructive surgeries between May 2018 and August 2020 were prospectively collected, and their respective intraoperative QHAG diameters measured and recorded. Pearson’s correlation test was employed to determine the correlation between the preoperative demographic and anthropometric data and the obtained corresponding graft diameters. Simple linear regression was performed to obtain the graphical plots and determine the relationship between the dependent and independent variables. Of these, the variables showing significant association were subjected to stepwise linear regression to identify and exclude the confounder(s) and obtain the predicted equation.Results2, mean thigh circumference was 50.4 cm, and the obtained mean graft diameter was 8.0 mm. A strongly positive correlation was observed between height and the graft diameter  and thigh circumference and the graft diameter . In contrast, weight showed a moderately positive correlation with the graft diameter . A very weakly positive correlation was observed between the BMI of the subjects and the obtained graft diameters . However, no correlation was observed between the age and the final graft diameters . Subsequent linear regression analysis indicates that only height  and the thigh circumference  share a significant predictive value for the obtained QHAG. Both height and thigh circumference together were good predictors for graft diameter as determined by multiple regression =272.372, P<0.001), with an R2 of 0.886.The study comprised 73 male participants. The study participants' mean age was found to be 33.7 years, mean height was 173.1 cm, mean weight was 71.2 kg, mean BMI was 23.7 kg/mConclusionCertain anthropometric parameters depict a positive correlation with the QHAG diameter and can assist in preoperative planning, predicting the possible harvested graft diameter and the need for alternative grafts or augmentation during ACL reconstructive surgeries. Injury to the anterior cruciate ligament (ACL) is one of the most common athletic injuries encountered globally . It is aThe graft used most often, i.e., the HT autograft, utilizes the semitendinosus and gracilis tendons, derived from the affected side, doubled up twice onto themselves to create a four-strand graft (the quadrupled hamstring autograft). It has been reported that the tensile strength of the graft used increases significantly with an increase in the graft diameter .Several studies have recommended the use of grafts with diameters equal to or greater than 8 mm, and that reconstruction with grafts lesser than 8 mm diameter has a higher risk of graft failures, poorer functional outcomes, and higher revision rates -16. OwinThis prospective study aimed to determine whether any correlation exists between the various demographic and anthropometric parameters like age, weight, height, body mass index (BMI), and thigh circumference, and the harvested quadrupled hamstring autograft intraoperatively in ACL reconstruction among male subjects of Indian origin. We hypothesized that no such correlation exists between the dependent and the independent variables to analyze whether the harvested graft size can be preoperatively predicted using anthropometric measurements in our study population.The study was conducted in a tertiary care center and teaching hospital in a district in central Uttar Pradesh, India. Approval of the study was acquired from the Institutional Ethics Committee, Uttar Pradesh University of Medical Sciences (Reference Number 125/2018). We used a prospective cohort study design to study the correlation of demographic and anthropometric data of subjects with the quadrupled hamstring autograft diameter in the ACL reconstruction. The enrollment of study subjects was done between May 2018 and August 2020 with appropriate written and informed consent.Study participantsPopulation Under StudyAll patients who present with a symptomatic acute ACL injury or a chronic ACL deficiency (categorized on the basis of time elapsed from injury till presentation) .  Inclusion CriteriaMale patients aged 17 years or more, presenting with an acute ACL injury who remained symptomatic after adequate rehabilitation , and patients with chronic ACL deficiency planned for primary ACL reconstruction using anatomical single-bundle quadruple HT autograft. Exclusion CriteriaFemales; revision ACL reconstruction surgeries; patients undergoing ACL reconstruction using grafts other than HTs; double-bundle hamstring graft reconstructions; ACL injuries associated with other significant complete ligamentous injuries; ACL injuries with associated meniscal injuries that required suturing; acute ACL injury with tibial spine avulsion.Study designWe adopted a purposive sampling strategy to obtain the sample size. From a sampling frame of 108 eligible patients who presented during the study duration and after exclusion of the subjects who did not fulfill the inclusion criteria, a total of 73 patients consented to the procedure and were enrolled to participate in the study (N=73)  and height (in cm) were recorded using the same weighing scale and stadiometer, respectively, for all the patients. The thigh circumference (in cm) of the affected side was measured using the same nonstretchable tape at a point 15 cm proximal to the superior pole of the patella, with the patient in supine position and the hip and the knee in full extension. The surgery was performed by the same certified orthopedic surgeon, trained and experienced in arthroscopic knee procedures, and both the semitendinosus and the gracilis hamstring grafts harvested using the same technique in all the patients. A standard 4-cm-long incision anteromedially over the proximal tibia was used to expose the pes anserinus for harvesting the hamstrings graft after releasing the tendons with an open-end tendon stripper. After separating muscle fibers from the tendons and trimming the tendons, a whipstitch was placed at both ends of each tendon with a nonabsorbable polyester suture. Then a four-strand graft was made by looping the derived tendons onto themselves. The final graft diameter measurement was then obtained by passing the graft through sizing cylinders (in increments of 0.5 mm) of the ACL reconstruction measurement guide (Arthrex). The diameter of the smallest calibrated sizing cylinder through which the entire graft could pass through smoothly was considered the final graft diameter. The operating surgeon, who was blinded from the anthropometric data, recorded the graft diameter intraoperatively. Single-bundle anatomic ACL reconstruction procedure was then carried out using standard techniques. Tightrope and interference screws were used as the femoral and tibial end fixation techniques, respectively, and these were kept similar in all the subjects. The relationship between the preoperatively measured anthropometric variables with the graft diameter obtained during surgery was then analyzed. Statistical analysisWe calculated the descriptive statistics of the various variables to describe the demographic profile of the population under study. The normality of the data distribution was ascertained using tests of normality. Pearson’s correlation test was used to determine whether there exists any correlation between anthropometric measurements (independent variables) and the obtained size of the quadrupled hamstrings autograft (dependent variable). The bivariate analysis further identified variables associated with graft diameter at a significance level of P<0.05. From this, the variables found to be associated at a P-value of <0.05 were further included in a stepwise linear regression to arrive at the predicted equation. Additionally, the potential confounder(s) were identified and excluded from the equation. A P-value of less than 0.05 (<5%) was considered statistically significant at a 95% confidence interval. All the outcome analyses were performed using the SPSS version 24.0 .A total of 73 male patients participated in the study. The means of the predictor and outcome variables, the anthropometric data, and the demographic profile of the study population are depicted in Table 2, and the mean thigh circumference was 50.4±6.8 cm. Out of the 73 patients, 30 (41.09%) had sustained an injury to their left knee, whereas 43 (58.9%) had their right knee injured. Road traffic accidents  were the most common mode of injury, followed by sports and athletics-related events   had a graft diameter of 8 mm or more, the most frequent size being 8 mm 23.3%, n=17)  and thigh circumference  with the graft diameter, a moderately positive correlation between patients’ weight  and the graft diameter, and a very faintly positive correlation between patients’ BMI  and the graft diameter. No significant correlation was obtained between the patients’ age  and the quadrupled hamstring graft diameter harvested , thigh circumference , and weight  are significant predictors of the final graft diameter, the strongest association being with the patients’ height. On the contrary, no significant relationship was observed between the age of the patients  with the intraoperatively obtained graft diameter, whereas BMI  showed only a weak association with the graft diameter +0.139 (height), where both height and thigh circumference were measured in centimeters. Participants’ graft diameter increased by 0.011 mm with each centimeter increase in thigh circumference and by 0.139 mm with each centimeter increase in height of the subjects, respectively. Both height and thigh circumference were significant predictors of graft diameter.A simple linear regression analysis was carried out, and the coefficient of determination was calculated for each independent demographic and anthropometric variable, keeping the obtained graft diameter as the dependent variable. It was determined that only height , thigh circumference , and weight  were significantly associated with the size of the graft diameter, with the height being the most strongly related. This strength of the relationship was justified to be strong, as up to 88.3% of the variance in the harvested graft diameter could be attributed to height, and thigh circumference could explain up to 59.1% of the variability in the graft diameter. In contrast, only 26.4% and 5.6% of the graft diameter variance could be attributed to weight and BMI, respectively. Age had no statistically significant relationship with the harvested graft diameter.Upon analysis of the study outcomes based on our study population of 73 Indian males undergoing primary ACL reconstruction, we observed a positive correlation between the height, thigh circumference, weight, and the BMI of the study subjects, with the diameter of harvested HT autograft. Of these variables, height and thigh circumference were found to have a strong correlation, weight was only moderately correlated, and BMI had a poor correlation with the obtained graft diameter. Patients' age showed no correlation with the graft diameter. Further analysis using linear regression showed that only height ; however, together with height, they showed a positive association with the dependent variable and a significant predictive value for harvested graft diameter, with an RAmong all the independent variables, height was determined to be the most significant predictor of harvested quadrupled hamstring graft diameter in ACL reconstruction. This stands in corroboration with multiple studies conducted previously ,21,26,27A significant correlation between the thigh circumference and the graft diameter of the subjects was observed in the preliminary analysis in our study, but upon further investigation using linear and multiple regressions, only a moderate predictive power for the graft diameter could be ascertained to the measured thigh circumference alone. This is in contrast to the findings of Treme et al. and Asif et al., who documented thigh circumference to be a significant predictor of the HT graft diameter ,20. GuptWe observed a weak correlation between the weight of the subjects and the size of grafts; however, upon multiple regression analysis, it was found to act as a confounder. Weight has also been reported to have no significant association with the graft diameter in other studies previously ,21. WherIt has previously been shown that the graft diameter is not related to BMI, as demonstrated in multiple separate studies ,24,26,27Studies involving both genders have demonstrated that females have a significantly smaller graft diameter than men ,26. TremOur findings strongly correlate with the similar studies undertaken previously on subjects of Indian origin, especially in regard to height having the strongest correlation and being the most significant predictor ,22,24,28LimitationsThis study does not take into account the possible differences in measuring the thigh circumference due to the position of the patient (supine or standing) and the site of measurement  and its possible effects on relationship with the final predicted graft diameter. Moreover, we measured the weight (and the BMI) of the study subjects, which do not address the varying body fat percentages in different individuals and can be a potential source of discrepancy. Future studies with measurements of lean body mass instead can be of help in this regard. Also, studies with larger sample sizes are needed to ascertain the definitive relationship between the variables under study.Preoperative measurements of certain anthropometric parameters can prove to be a valuable tool for predicting the adequacy of intraoperatively harvested graft diameter, the need for augmentation or alternative grafts, and the risk of failure or the graft used. This can further help reduce the operation time, postoperative pain, and scar if an alternative graft is chosen due to inadequacy.Height remains the most consistent parameter among the variables studied for the prediction of the harvested quadrupled hamstrings autograft diameter, even in the study population of Indian males. The predictive value was seen to improve further when thigh circumference and height are used in combination.


Retrogradation is the principal cause for bread staling and, therefore, it has attracted a lot of interest from the food industry. In this study, the inhibitory effect of citrus peel hydrolysates (CPH) on retrogradation of wheat starch (WS) in the presence of sucrose was investigated. The pasting properties showed that further addition of CPH caused a lower setback value than the addition of sucrose alone. Hardness of the gel, retrograded at 4 °C for five days, showed a similar tendency, which was reduced more in CPH addition than WS itself or sucrose addition alone. The low retrogradation enthalpy of the CPH including starch gel also indicated the positive effect of CPH on retarding retrogradation. These results suggested that incorporation of CPH in starch-based foods would be effective for inhibiting retrogradation, preventing the deterioration of the quality of food products. Starch is the main component of wheat flour, accounting for 80 g/100 g . Starch Generally, starch is gelatinized before being consumed as food, either during processing or cooking . Starch Retrogradation of starchy foods occurs during food storage. It results in a decrease in water retention capacity and digestibility, and negatively affects the quality of starch-containing food products by destroying the texture and increasing the hardness, opacity, and fragmentation and, therefore, finally affects the storage stability of products . Starch Most starchy foods contain a considerable amount of sugar, especially sucrose, for taste and stability modification, and, therefore, the effect of sucrose on starch properties such as gelatinization and/or retrogradation has been previously investigated ,11,12,13Citrus unshiu were purchased from a local market at Jeju in the Republic of Korea. The pectinases, Pectinex Ultra SP-L and Pectinex Ultra Pulp, were purchased from Novozymes A/S . Wheat starch was purchased from Sigma-Aldrich .g for 10 min). The supernatant was precipitated with ethyl alcohol (75%) for 16 h. The mixture was centrifuged (1500× g for 10 min) and the supernatant was lyophilised. Extraction yield (%) was calculated as a percentage of the weight of the recovered hydrolysate powder to the weight of the initial citrus peel powder.Citrus (C. unshiu) peels were dried in an oven at 45 °C. The dried peels were milled using an electric grinder and filtered using a filter sieve to obtain a powdered sample. The citrus peel powder was thoroughly rinsed with distilled water (DW) to remove pigments. Extraction was carried out using two different enzymes for varying durations of enzyme treatment. The resulting solid (solid–liquid ratio of 1:20) was hydrolysed in DW adjusted to pH 4.5 containing 1% Pectinex Ultra Pulp or Pectinex Ultra SP-L and stirred for 3 h or 12 h at 45 °C. The hydrolysates were heated at 100 °C for 10 min to inactivate the enzymes. After enzyme inactivation, the mixture was filtered and centrifuged  system connected to a Superdex 75 10/300 GL packed column  and a refractive index detector (Agilent). Ammonium formate buffer  was used for elution at a flow rate of 0.5 mL/min.TM PA1 column . The flow rate was a constant 1.0 mL/min and the volume injected was 25 μL. The acidic sugars were eluted with a gradient solvent system using a mobile phase consisting of A (150 mM NaOH) and B (150 mM NaOH with 600 mM NaCH3CO2) [The monosaccharide composition of CPH was analyzed using high-performance anion exchange chromatography coupled with a pulse amperometric detector (HPAEC-PAD). CPH was separated on a CarboPacing of A 0 mM NaOHaCH3CO2) .The CPH obtained by incubation with Pectinex Ultra Pulp for 12 h was employed to further investigate the effect on the retrogradation property of WS.w/v) suspension) in an RVA aluminium canister, which served as a control. The compositions of the various groups were as follows: Group 2 (WS + sucrose), 0.6 g of sucrose was added to 3 g of WS; Group 3 (WS + sucrose + CPH10) and Group 4 (WS + sucrose + CPH20); 0.6 g of sucrose and 0.3 g or 0.6 g of CPH were added, respectively. The test profile was programmed according to the standard pasting method.The effect of CPH on the pasting properties of WS was determined using Rapid Visco Analyser . The samples were classified into four groups based on the addition of sucrose and CPH. WS slurry was initially prepared by dispersing 3 g (dry basis) WS into 25 g DW  mode. The starch pastes that were produced after RVA measurement were cooled to be set as starch gel and then stored at 4 °C for zero, one, three, and five days for retrogradation. The size of the gel used for TPA was 5.0 cm × 2.0 cm (diameter × height). The gels were compressed twice with a cylinder probe with 25 mm diameter at a test speed of 0.5 mm/s. Compression of the starch gel was set to 50% of the original sample height. The textural parameters of hardness were calculated from the TPA curves.The starch pastes produced via RVA were stored at 4 °C for five days and were lyophilized. The powered sample and distilled water was weighed into a stainless-steel pan at the ratio of 1:3. The pan was hermetically sealed and then kept at room temperature overnight for moisture equilibrium. Thermal analysis of the retrograded starch gels was performed using a differential scanning colorimeter . The scan was conducted from 25 °C to 95 °C at a 10 °C/min scanning rate, with an empty pan as a reference. The onset, peak, and end temperatures and enthalpies corresponding to retrogradation were measured.p value < 0.05 were considered significant.Data are expressed as mean ± standard deviation (SD), and the samples were analyzed via a one-way analysis of variance using SAS, version 8.1 . Differences with a Extraction yields of CPH after treatment with the two enzymes are presented in The molecular distributions of CPH observed via HPLC separation were presented in We evaluated the effect of CPH on the pasting properties of WS by RVA, and the results are presented in Breakdown is associated with the stability of starch paste . The breSetback viscosity values depend on the difference between trough viscosity and final viscosity, which results from the rearrangements between amylose and amylopectin when the temperature was decreased from 95 °C to 50 °C . TherefoStarch retrogradation is a major factor in the staling of bread and rice cake, and is thought to affect textural properties, for example, hardness . TherefoWe measured the thermal properties of gel stored at 4 °C for five days to analyze the retrogradation characteristics by DSC . Starch DSC analysis reflects the property of the double helical structure and the hydrogen bonds that stabilize the double helical structure. The melting temperature indicates the structural stability of crystallites of the degree of the order of double helices, where changes in ΔH indicate the energy required for thermal transition of double helices and the resultant crystallites .The onset, peak, and end temperatures of the lyophilized gels were revealed over the temperature range of 54.19–59.54 °C, with no significant difference among samples. However, a difference according to the addition of sugar and CPH was observed in ΔH values, which reflect the different degree of retrogradation. After five days of storage, the ΔH value of WS was 0.354 J/g and that of WS + sucrose gel was 0.367 J/g. The addition of CPH by 10% and 20% resulted in a significant decrease in retrogradation enthalpy of 0.178 J/g and 0.212 J/g, respectively. These values corresponded to 74% and 63% of the ΔH from WS + sucrose gel. A lower ΔH value indicates that a smaller amount of crystalline structure, as well as the double helical structure which originated from the hydrogen bonds regenerated during retrogradation, was formed in starch gels that included CPH. Therefore, compared with WS itself or WS with only sucrose added, retrogradation was retarded when CPH was also included. This result corresponded with RVA pasting properties  and gel hardness.The fundamental principle of starch retrogradation is the conversion of hydrogen bonds between the starch molecule and the water molecule into hydrogen bonds among the starch molecules . TherefoCPH was prepared by the enzymatic hydrolysis of citrus peel, and its effects on the retrogradation of starch paste, including sucrose, were examined. The CPH was composed of various monosaccharides where arabinose, glucose, and galacturonic acid were dominant (78–80%). Though sucrose addition did not have a positive effect on retarding retrogradation, further addition of CPH significantly inhibited the retrogradation, as supported by the lower setback value (RVA), lower retrograded gel hardness, and lower retrogradation enthalpy. This research showed that adding CPH to starch-based foods, particularly sucrose-containing products such as cake and sweet dough bread, is effective for inhibiting retrogradation. Therefore, CPH could be utilized as a novel food ingredient in the form of an anti-staling agent to stabilize food quality for a longer storage time.


Incorporating fiber at high levels (>10%) into direct-expanded products with acceptable texture is challenging. Fundamental explanations for the interaction of starch and fiber and the cause of expansion reduction need further understanding for the effective incorporation of fiber into expanded products. This study aims to explain how cellulose content impacts the physicochemical properties of starch-based extrudates and the long-range and short-range molecular changes of starch. Mixtures of cornstarch (50% amylose) and cellulose were extruded using a co-rotating twin-screw extruder. Thermal and pasting properties of the raw mixtures were evaluated, and the physicochemical properties and microstructure of extrudates were determined. Long-range and short-range molecular changes of starch-cellulose mixtures before and after extrusion were observed by X-ray Diffraction (XRD) and Fourier Transform Infrared (FTIR) spectroscopy. The expansion ratio of extrudates reduced significantly as the cellulose content increased and had a strong negative correlation with crystallinity. Cell structures of starch-cellulose extrudates had a smaller and more uniform pore size but possessing a more ruptured matrix. FTIR spectra suggested that there was no covalent bonding interaction between starch and fiber after extrusion. Extrusion reduced the overall crystallinity compared to the raw mixtures. XRD showed that the crystallinity of the starch-cellulose extrudates increased as the cellulose content increased, and the XRD peaks representing cellulose remained unchanged. Cellulose could interfere with starch chain reassociation through intermolecular hydrogen bonding during the expansion process. Phase separation of starch and cellulose is likely to occur at high cellulose content, which could be another reason for the reduced expansion.  •FTIR showed no covalent bonding interactions between starch and cellulose.•Crystallinity of extrudates increased with increased cellulose content.•Expansion is negatively correlated with crystallinity.•Cellulose interferes with the reassociation of starch biopolymers.•Phase separation of starch and cellulose is likely to occur during extrusion. However, the production of high-fiber extruded products is still challenging, especially with those incorporating insoluble fiber. Many high-fiber foods are not well-accepted by consumers, mainly because of their poor sensory attributes . RefinedSignificant material changes occur during the extrusion process when comparing the raw inputs to the final product exiting the die, including molecular degradation, phase change, material flow, and rearrangement of molecular structures due to the shear, heat, and pressure of the extruder. Extensive studies on the behavior of starch in the extruder have been conducted for over 50 years though relatively fewer studies on fiber have been reported. Hence, the study of the behavior of starch-fiber combination is more complicated. The behavior of individual starch and fiber compositions needs to be studied so that mixed compositions can be explained to facilitate new approaches or strategies for achieving desired food qualities. However, the interaction of components within a food matrix is complex, and many have not been unveiled. Many studies have explored the effects of fiber directly on product properties . Some stAcceptable high-fiber products can be produced when the effects of fiber on molecular and functional changes of starch-fiber mixtures under extrusion conditions can be identified. Thus, there is a need to understand the physical and chemical changes of starch-fiber mixtures during extrusion. This information can help explain the fundamental interactions between starch and fiber, and the causes of reduced expansion. This information could further be utilized to make high-fiber expanded products with a better texture. Thus, this study aimed to investigate how the cellulose interacts physically and molecularly with the starch in the extrusion process.22.1Cornstarch with 50% amylose content (S50) was obtained from Ingredion, Incorporated . This cornstarch was selected because we found in our previous study that the inclusion of cellulose in cornstarch with 50% amylose content resulted in a higher expansion compared to other cornstarch types . Powdere2.2Mixtures of starch and cellulose were prepared with different cellulose contents: 0% (CL0), 5% (CL5), 15% (CL15) and 30% (CL30). The blends were then mixed with distilled water using a Hobart mixer  to obtain a final moisture content of 18 ± 0.5% (w.b.). All samples were stored at 4 °C overnight for moisture equilibration.The mixtures were extruded using a co-rotating twin-screw extruder , with a 20-mm screw diameter and a length-to-diameter ratio (L/D) of 19.5:1. A round die (diameter of 3.15 mm) was used, and the screw profile used in this study is shown in Supplementary material . The tem2.3°C/min, a 5-min hold at 95 °C, and a 2-min hold at 50 °C.Pasting properties of raw samples were measured by a Micro Visco-Amylo-Graph (MVAG)  according to Thermal analysis of raw samples was performed using Differential Scanning Calorimetry (DSC) . Each mixture (10.0 ± 1 mg) was combined with 50 μL of distilled water in a stainless-steel sample pan . Sample pans were then sealed with a crimper and equilibrated overnight at 4 °C. A pan with 50 μL of distilled water was used as a reference. The pans were heated from 30 to 160 °C at a rate of 5 °C/min. All tests were run in triplicate.2.4Expansion ratio (ER) is the ratio of the radial diameter of extrudates and die diameter. The radial diameter of extrudates was measured using a caliper . For each condition, the expansion ratio of an extruded sample was recorded as the average of 20 random measurements. Water Absorption Index (WAI) and Water Solubility Index (WSI) analyses followed the methods described by 2.5Surface and cross-sections of selected extruded samples were cut by a precision blade. Samples were fixed on holders using conductive carbon tape. The fixed samples were sputter-coated with gold to improve their conductivity and viewed under a Scanning Electron Microscope (SEM)  in a pressurized chamber (30 Pa) at an accelerating voltage of 30 kV. Multiple areas of a cross-section of an extruded sample were observed for overall cell structure pattern and ruptured or collapsed cell structures. Smoothness, wavy structure, or ruptured surfaces were observed for the surface of a sample. All extrudate samples were observed at magnifications of x30, x60, and x200, and raw flours and ground extrudates were observed at a magnification of x500.2.6X-ray diffraction spectra of raw and extruded samples were measured using an X-ray diffractometer (XRD)  at 40 kV and 15 mA with Cu Kα radiation. Samples were scanned over a range of 2θ from 2 to 40° at the rate of 2°/min with a step size of 0.02. Spectra data were processed using OriginLab Software . The relative crystallinity of samples was calculated according to , using E2.7−1 for 128 scans. The spectra resolution was 4 cm−1. All spectra were analyzed using Omnic Sofware, the built-in program of Nicolet iS10. The spectra were baseline corrected by drawing a straight line between 1200 and 800 cm−1. The absorbance intensity at 995, 1015, and 1045 cm−1 from the baseline was collected for each sample. The ratio of the absorbance intensities: 1045/1015 cm−1 and 995/1015 cm−1 were calculated for the comparison of short-range conformation of the samples as described in . A sample was scanned between the wavenumber range of 4000 - 600 cmribed in .2.8P < 0.05). The Pearson correlation coefficient analysis between cellulose content, crystallinity, FTIR peak ratio, and the physical properties of extrudates was also performed. These analyses were conducted using SPSS software .Analysis of Variance (ANOVA) was used to analyze the mean differences between the extrusion process responses and extrudate characteristics. The normality of data was assessed by the Shapiro-Wilk test, and the comparison of means was assessed by Tukey's test with the defined significance of 5% (33.1paste) of 89 °C, while cellulose did not have a Tpaste. Cellulose is insoluble, and it was not disrupted to a large degree by the temperature in MVAG. As the cellulose content increased, Tpaste of the mixtures increased from 89.3 °C to 92.7 °C, and their peak viscosity (PV) and final viscosity (FV) decreased. The peak viscosity of the sample with 15% cellulose was reduced by almost half compared to the pure starch. The decrease of PV due to increasing fiber content was also reported in the starch-sugarcane bagasse study (se study .Table 1Po and Tp) as the cellulose content increased (P > 0.05). However, the melting enthalpy decreased as cellulose content increased. It could be attributed to the pure cellulose not undergoing any phase changes at these conditions  of extrudates reduced from 3.3 ± 0.1 to 1.9 ± 0.1 at 150 rpm, and from 3.6 ± 0.1 to 1.9 ± 0.0 at 250 rpm, as the cellulose content increased from 0% to 30%, respectively . The ER Water Absorption Index (WAI) also showed a similar trend as ER. It decreased as the cellulose content increased but was not significantly different between 150 rpm and 250 rpm for each of the cellulose levels. This result is in agreement with several previous reports that concluded, increasing fiber contents decreased WAI of extrudates . In contWSI increased as the expansion ratio increased because of the degradation of starch. WSI slightly increased at 5% and 15% (w/w) cellulose contents and then decreased at 30% (w/w) of cellulose . Kallu e3.33.4XRD diffractograms show the changes in the crystalline structure of raw and extruded mixtures. In 3.5−1. Band assignments for raw starch and cellulose are shown in the supplementary material  and decreases during reordering (from gelatinized to retrograded starch). Peak 995 cm−1 is also associated with the crystalline structure, especially for native starch, and is sensitive to water content and related to intramolecular hydrogen bonding  was wider compared to the extrudates without cellulose (CL0). This peak is sensitive to structural changes and is associated with hydrogen bonding; thus, the result suggests the interference of cellulose with starch reassociation (retrogradation) in the extrudates.To clearly illustrate the changes in these peaks, 3.6−1 decreased after extrusion (1.17 for raw starch to 1.06-1.03 for extrudates), which explained the destruction of native starch order structure after extrusion. The XRD data supported this result because the crystallinity of all samples reduced after extrusion. −1 (995/1015 cm−1 in this study) compared to the extruded starch.Ratios of the peaks in FTIR spectra, 995/1015 and 1045/1015 , have been studied as indexes for the short range order of molecules, indicating the degree of order in starch molecules . In this−1 of extrudates decreased as the cellulose content increased. Also, −1 of starch-cellulose extrudates had a strongly negative correlation with the crystallinity of extrudates . This result is contradicted with the previous studies on extruded starch alone  to 0.52 (extruded starch), but this ratio for the extruded samples increased as the cellulose content increased . −1 and the ordered structure of starch by XRD. Therefore, this peak ratio may be of less interest compared to the peak ratio 995/1015 cm−1 to study the molecular changes in starch and cellulose by FTIR.The peak ratio 1045/1015 cmncreased . There wER was strongly negatively correlated to crystallinity , which means increasing crystallinity of the materials decreased the ER of extrudates. SME also had a negative correlation with crystallinity, even though the correlation was not significant. In general, SME affected the degree of starch degradation . However4The presence of cellulose significantly affected the physicochemical properties of extrudates. Increased cellulose content reduced the expansion ratio of extrudates with smaller porous cell structures. Peak melting temperatures of materials remained unchanged with the increasing cellulose inclusion, suggesting that cellulose is resistant to breakdown and did not go through any phase change under the conditions studied. Results from FTIR suggested that no covalent bonding interaction between starch, fiber, and water existed under extrusion conditions but that their interactions are mainly due to the hydrogen bonding. Further, fiber may interfere with how starch biopolymers reassociate through intermolecular hydrogen bonds. XRD results supported that cellulose did not undergo a great extent of molecular changes as starch did. The effects of cellulose on physicochemical properties could mainly be attributed to a likely phase separation between starch and cellulose in the extruder  and the disruption of intermolecular hydrogen bonding of starch by cellulose during the expansion at the die exit. Further studies of extrusion with higher cellulose content greater than 30% may help to explain clearly the structural and molecular changes of cellulose. Also, the rheological studies of starch-cellulose mixtures may be useful for explaining the phase separation phenomenon. At the microstructural level, color staining microscopic methods such as confocal microscopy should be performed to confirm that cellulose fiber acts as a filler within the cell walls of extrudates and/or interfere with starch melt to form cells of extrudates.Pichmony Ek: Conceptualization, Methodology, Formal analysis, Investigation, Writing – original draft, Visualization. Bon-Jae Gu: Methodology, Investigation, Writing – review & editing. Steven R. Saunders: Writing – review & editing. Kerry Huber: Writing – review & editing. Girish M. Ganjyal: Conceptualization, Writing – review & editing, Supervision, Project administration, Funding acquisition.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.