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Chronic wounds are non-healing lesions characterized by a high degree of inflammation, posing significant challenges in clinical management due to the increased risk of severe infection. This study focuses on developing a powder for cutaneous application to enhance the healing and prevent infections in chronic wounds. The smart nanocomposites-based biomimetic microparticles here developed combine the properties of chitosan and of clays and represent a significant innovation in the field of biomaterials for skin regeneration since they possess enhanced antimicrobial properties, are multi-functional scaffolds and promote cell proliferation, support tissue reconstruction by mimicking the natural extracellular matrix, and provide hemostatic properties to control bleeding during wound closure. The microparticles were made of chitosan and doped with clay minerals, specifically montmorillonite or layered double hydroxides, containing copper ions. The synergistic combination of biomimetic polymers and clays aims to regulate cellular responses, angiogenesis, and extracellular matrix (ECM) deposition, leveraging the bioactive properties of both components to promote wound healing. Montmorillonite and layered double hydroxides were enriched with copper ions through intercalation or coprecipitation methods, respectively. The water-insoluble microparticles were prepared using a chitosan derivative, chitosan carbamate, synthesized to obtain chitosan-based microparticles via spray-drying without crosslinkers. Physico-chemical characterization confirmed the successful doping of Cu-clay interaction products in the microparticles. In addition to enhanced cell proliferation and hemostatic properties, the presence of Cu-clays boosted the microparticles' antibacterial properties. Encouraging preclinical in vitro and in vivo results suggest that these smart nanocomposite biomimetic microparticles doped with Cu-enriched clay minerals could be promising candidates for simultaneously enhancing healing and controlling infections in chronic wounds., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giuseppina Sandri reports financial support was provided by The National Recovery and Resilience Plan (NRRP). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

We measured the average group refractive index (RI) of 120 isolated lenses from 120 human donors (age: 0.03 to 61 years). The average group RI was calculated from a measurement of the optical thickness of the lens using optical coherence tomography and the apparent window shift of the test chamber caused by the lens. The estimated measurement uncertainty was ±0.004. The group RI at 880 nm was converted to phase RI at 589 nm using the dispersion equation of water and protein. From 2 to 61 years, the mean value of the RI was 1.415 ± 0.002 (group index at 880 nm) and 1.406 ± 0.002 (phase index at 589 nm) independent of age (p = 0.774). Two lenses from donors of age 0.33 and 3 months had significantly lower RI (group index: 1.405 and 1.403; phase index: 1.396 and 1.394). From age 2 to 61, the average lens RI is constant with age within the measurement uncertainty (±0.004)., Competing Interests: There are no financial interests to disclose., (© 2024 Optica Publishing Group.)

Carob pulp flour has antidiabetic and antioxidant activities, is naturally sweet, and is rich in fibers. It is obtained from carob pod pulp from the evergreen tree Ceratonia siliqua L., which is grown in Mediterranean areas and is known for locust bean gum production. Despite its valuable effects on health, such as the modulation of the glycemic index, this ingredient has a tremendous impact on technological and hedonic features, mainly on color, flavor, and texture. In this paper, the qualitative features and consumers' acceptance of a carob-based gluten-free bakery product where rice flour was substituted at 40% with carob pulp flour were studied. A panel group of experts described the bread as dark, quite dense, sweet, aromatic, and with a limited bubble dispersion. On the other hand, the sensory assessment and the willingness to pay of consumers were assessed in two groups (a fully informed one about heathy attributes of the food and a blind one). The results indicated a moderate appreciation of the overall quality of the product (average score between 4 and 5 points on a 9-point Likert scale). The information about the food's healthy properties and the ability to maintain a low glycemic index did not enhance the consumers' perception of the product, while previous knowledge and involvement in the product consumption were perceived to have primary importance regarding the final consumers' choice. Finally, an accelerated shelf-life test was run on the packaged snack to evaluate the general quality and stability. The protective packaging helped in limiting bread decay and maintaining the textural characteristics.

Previous studies have shown that pharmaceutical agents such as lipoic acid have the ability to soften the lens, presenting a promising avenue for treating presbyopia. One obstacle encountered in the preclinical stage of such agents is the need for precise measurements of lens elasticity in experimental models. This study aimed to evaluate the effects of 25-hydroxycholesterol, lipoic acid, and obeticholic acid on the viscoelastic properties of mouse lenses using a custom-built elastometer system. Data were acquired on lenses from C57BL/6J female mice from two age groups: young (age: 8-10 weeks) and old (age: 32-43 weeks). OD lenses were used as the control and OS lenses were treated. Control lenses were immersed in Dulbecco's Modified Eagle Medium (DMEM) and treatment lenses were immersed in a compound solution containing 25-hydroxycholesterol (5 young and 5 old), lipoic acid at 2.35 mM (5 young and 5 old), lipoic acid at 0.66 mM (5 old), or obeticholic acid (5 old) at 37 °C for 18 h. After treatment, the mouse lenses were placed in a DMEM-filled chamber within a custom-built elastometer system that recorded the load and lens shape as the lens was compressed by 600 μm at a speed of 50 μm/s. The load was continuously recorded during compression and during stress-relaxation. The compression phase was fit with a linear function to quantify lens stiffness. The stress-relaxation phase was fit with a 3-term exponential relaxation model providing relaxation time constants (t 1 , t 2 , t 3 ), and equilibrium load. The lens stiffness, time constants and equilibrium load were compared for the control and treated groups. Results revealed an increase in stiffness with age for the control group (young: 1.16 ± 0.11 g/mm, old: 1.29 ± 0.14 g/mm) and relaxation time constants decreased with age (young: t 1  = 221.9 ± 29.0 s, t 2  = 24.7 ± 3.8 s, t 3  = 3.12 ± 0.87 s, old: t 1  = 183.0 ± 22.0 s, t 2  = 20.6 ± 2.6 s and t 3  = 2.24 ± 0.43 s). Among the compounds tested, only 25-hydroxycholesterol produced statistically significant changes in the lens stiffness, relaxation time constants, and equilibrium load. In conclusion, older mouse lenses are stiffer and less viscous than young mouse lenses. Notably, no significant change in lens stiffness was observed following treatment with lipoic acid, contrary to previous findings., Competing Interests: Declaration of competing interest The research described in this project was funded in part by AbbVie. S. Cabrera-Ghayouri and M. Dibas are employees of AbbVie., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Patients with essential thrombocythemia (ET) are treated with once-daily low-dose aspirin to prevent thrombosis, but their accelerated platelet turnover shortens the antiplatelet effect. The short-term Aspirin Regimens in EsSential Thrombocythemia trial showed that twice-daily aspirin dosing restores persistent platelet thromboxane (TX) inhibition. However, the long-term pharmacodynamic efficacy, safety and tolerability of twice-daily aspirin remain untested. We performed a multicenter, randomized, open-label, blinded-endpoint, phase-2 trial in which 242 patients with ET were randomized to 100 mg aspirin twice- or once-daily and followed for 20 months. The primary endpoint was the persistence of low serum TXB 2 , a surrogate biomarker of antithrombotic efficacy. Secondary endpoints were major and clinically relevant non-major bleedings, serious vascular events, symptom burden assessed by validated questionnaires, and in vivo platelet activation. Serum TXB 2 was consistently lower in the twice-daily versus once-daily regimen on 10 study visits over 20 months: median 3.9 ng/mL versus 19.2 ng/mL, respectively; p < .001; 80% median reduction; 95% CI, 74%-85%. No major bleeding occurred. Clinically relevant non-major bleedings were non-significantly higher (6.6% vs. 1.7%), and major thromboses lower (0.8% vs. 2.5%) in the twice-daily versus once-daily group. Patients on the twice-daily regimen had significantly lower frequencies of disease-specific symptoms and severe hand and foot microvascular pain. Upper gastrointestinal pain was comparable in the two arms. In vivo platelet activation was significantly reduced by the twice-daily regimen. In patients with ET, twice-daily was persistently superior to once-daily low-dose aspirin in suppressing thromboxane biosynthesis and reducing symptom burden, with no detectable excess of bleeding and gastrointestinal discomfort., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

The high rate of rejection and failure of orthopedic implants is primarily attributed to incomplete osseointegration and stress at the implant-to-bone interface due to significant differences in the mechanical properties of the implant and the surrounding bone. Various surface treatments have been developed to enhance the osteoconductive properties of implants. The aim of this work was the in vitro characterization of titanium alloy modified with a nanocrystalline hydroxyapatite surface layer in relative comparison to unmodified controls. This investigation focused on the behavior of the surface treatment in relation to the physiological environment. Moreover, the osteogenic response of human osteoblasts and adipose stem cells was assessed. Qualitative characterization of cellular interaction was performed via confocal laser scanning microscopy focusing on the cell nuclei and cytoskeletons. Filipodia were assessed using scanning electron microscopy. The results highlight that the HA treatment promotes protein adhesion as well as gene expression of osteoblasts and stem cells, which is relevant for the inorganic and organic components of the extracellular matrix and bone. In particular, cells grown onto HA-modified titanium alloy are able to promote ECM production, leading to a high expression of collagen I and non-collagenous proteins, which are crucial for regulating mineral matrix formation. Moreover, they present an impressive amount of filipodia having long extensions all over the test surface. These findings suggest that the HA surface treatment under investigation effectively enhances the osteoconductive properties of Ti6Al4V ELI.

The development of acute kidney injury (AKI) in polytrauma patients is a common and serious complication, with an incidence ranging from 6% to 50%. Polytrauma is a complex pathological condition that involves the collaboration of various specialists. On one hand, hemodynamic stabilization through fluid therapy and aminic support, with specific attack protocols, managed by anesthetists. On the other hand, if necessary, the initiation of renal replacement therapy such as Continuous Renal Replacement Therapy (CRRT), managed by nephrologists. CRRT is chosen both for managing fluid balance and ensuring the removal of toxic substances, as well as for proper control of electrolytes and acid-base balance., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Purpose: To quantify the angular dependence of monofocal intraocular lens (IOL) power., Setting: Ophthalmic Biophysics Laboratory, Kallam Anji Reddy campus, L V Prasad Eye Institute, Hyderabad, India., Design: Laboratory study., Methods: Experiments were performed on IOLs from 2 different manufacturers (APPALENS 207, Appasamy Associates and SN60WF, Alcon Laboratories, Inc.). IOL powers ranged from 17 to 25 diopters (D). The IOLs were mounted in a fluid-filled chamber, and the on-axis and off-axis powers were measured using a laser ray tracing system over the central 3 mm zone with delivery angles ranging from -30 to +30 degrees in 5-degree increments. The position of the best focus was calculated for each IOL at each angle. The angular dependence of IOL power was compared with theoretical predictions., Results: Peripheral defocus increased significantly with increasing incidence angle and power. The peripheral defocus at ±30 degrees increased from 5.8 to 8.5 D when the power increased from 17.5 to 24.5 D for APPALENS 207 and from 4.9 to 7.4 D when the power increased from 17 to 25 D for SN60WF. The mean difference between the measured and theoretical tangential power at ±30 degrees was 0.50 ± 0.16 D for the APPALENS 207 and -0.40 ± 0.10 D for the SN60WF, independent of IOL power., Conclusions: IOLs introduce a significant amount of peripheral defocus which varies significantly with IOL power and design. Given that peripheral defocus is related to lens power, replacement of the crystalline lens (approximately 24 D) with an IOL will produce a significant difference in peripheral defocus profile after surgery., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Nowadays, chronic wounds are the major cause of morbidity worldwide and the healthcare costs related to wound care are a billion-dollar issue; chronic wounds involve a non-healing process that makes necessary the application of advanced wound dressings to promote skin integrity recovery. Functionally Graded Scaffolds (FGSs) are currently driving interest as promising candidates in mimicking the skin tissue environment and, thus, in enhancing a faster and more effective wound healing process. Aim of the present work was to design and develop a porous FGS based on κ-carrageenan (κCG) for the management of chronic skin wounds; a freeze-drying process was optimized to obtain in a single-step a three-layered FGS characterized by a pore size gradient functional to mimic the structure of native skin tissue. In addition to κCG, arginine and whey protein isolate were used as multifunctional agents for FGS preparation; these substances can not only intervene in some stages of wound healing but are able to establish non-covalent interactions with κCG, which were responsible for the production of layers with different pore size, water content capability and mechanical properties. Cell migration, adhesion and proliferation within the FGS structure were evaluated in vitro on fibroblasts and FGS wound healing potential was also studied in vivo on a murine model., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier B.V.)

Accommodation is the process by which the eye changes focus. These changes are the result of changes to the shape of the crystalline lens. Few prior studies have quantified the relation between lens shape and ocular accommodation, primarily at discrete static accommodation states. We present an instrument that enables measurements of the relation between changes in lens shape and changes in optical power continuously during accommodation. The system combines an autorefractor to measure ocular power, a visual fixation target to stimulate accommodation, and an optical coherence tomography (OCT) system to image the anterior segment and measure ocular distances. Measurements of ocular dimensions and refraction acquired dynamically on three human subjects are presented. The individual accommodative responses are analyzed to correlate the ocular power changes with changes in ocular dimensions., Competing Interests: The University of Miami and authors MR, FM, and JMP stand to benefit from intellectual property in the OCT technology used in this study., (© 2024 Optica Publishing Group.)

Chronic wounds represent silent epidemic affecting a large portion of the world population, especially the elders; in this context, the development of advanced bioactive dressings is imperative to accelerate wound healing process, while contrasting or preventing infections. The aim of the present work was to provide a deep characterization of the functional and biopharmaceutical properties of a sustainable thin and flexible films, composed of whey proteins alone (WPI) and added with nanostructured zinc oxide (WPZ) and intended for the management of chronic wounds. The potential of whey proteins-based films as wound dressings has been confirmed by their wettability, hydration properties, elastic behavior upon hydration, biodegradation propensity and, when added with nanostructured zinc oxide, antibacterial efficacy against both Gram-positive and Gram-negative pathogens, i.e. Staphylococcus aureus and Escherichia coli. In-vitro experiments, performed on normal human dermal fibroblasts, confirmed film cytocompatibility, also revealing the possible role of Zn 2+ ions in promoting fibroblast proliferation. Finally, in-vivo studies on rat model confirmed film suitability to act as wound dressing, since able to ensure a regular healing process while providing effective protection from infections. In particular, both films WPI and WPZ are responsible for the formation in the wound bed of a continuous collagen layer similar to that of healthy skin., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier B.V.)

We present proof of concept for a handheld contact-type system capable of simultaneous optical coherence tomography (OCT) imaging of the retina and wide-field digital fundus color photography. The study focuses on demonstrating the feasibility of the proposed approach, particularly for eventual use in pediatric patients during examination under anesthesia in the operating room and in the neonatal intensive care unit. Direct contact of the probe with the cornea allows the photographer to maintain a stable position during imaging, reducing motion artifacts in the OCT images. Additionally, it simplifies the alignment process and increases the field of view of the optics. By integrating OCT and fundus imaging into a single device, the proposed compact modular design eliminates the need for separate, space-consuming systems dedicated to each imaging modality., Competing Interests: The University of Miami and some of the authors (MR, FM, JMP) stand to benefit from intellectual property in the technology used in this study., (© 2024 Optica Publishing Group.)

Abstract: A debate exists regarding which type of corticosteroids (standard-dose prednisone [PDN] or high-dose dexamethasone [HD-DXM]) is the best first-line treatment for adult patients with newly diagnosed untreated primary immune thrombocytopenia (pITP). An ad hoc study compared PDN with HD-DXM in newly diagnosed untreated patients with pITP (aged ≥18 but ≤80 years, platelet count of ≤20 or >20 but <50 × 109/L, and bleeding score of ≥8). Patients were randomised to receive PDN 1 mg/kg per day from days 0 to 28 (Arm A) or HD-DXM 40 mg per day for 4 days, every 14 days, for 3 consecutive courses (Arm B). Fifty-nine of 113 patients (52.2%) were randomized to Arm A and 54 of 113 (47.8%) to Arm B. In evaluable patients, total initial responses (complete response [CR], partial response [PR], minimal response [MR]) were 44 of 56 (78.57%) in Arm A and 46 of 49 (93.88%) in Arm B at days 42 and 46, respectively (P = 0.0284). Total final responses (at day 180 from initial response) were 26 of 43 (60.47%) in Arm A and 23 of 39 (58.97%) in Arm B (P = 0.8907). Total persistent responses (at 12 months from initial response) were 25 of 31 (80.65%) in Arm A and 20 of 36 (55.56%) in Arm B (P = 0.0292). Seven relapses occurred. Median follow-up was 44.4 months. Overall survival was 100% at 48 months, overall disease-free survival was 81.11% at 48 months from day 180. PDN and pulsed HD-DXM were well tolerated; HD-DXM allows effective initial responses but less long lasting than PDN. This trial was registered at www.clinicaltrials.gov as #NCT00657410., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Tendon disorders are common injuries, which can be greatly debilitating as they are often accompanied by great pain and inflammation. Moreover, several problems are also related to the laceration of the tendon-to-bone interface (TBI), a specific region subjected to great mechanical stresses. The techniques used nowadays for the treatment of tendon and TBI injuries often involve surgery. However, one critical aspect of this procedure involves the elevated risk of fail due to the tissues weakening and the postoperative alterations of the normal joint mechanics. Synthetic polymers, such as thermoplastic polyurethane, are of special interest in the tissue engineering field as they allow the production of scaffolds with tunable elastic and mechanical properties, that could guarantee an effective support during the new tissue formation. Based on these premises, the aim of this work was the design and the development of highly porous 3D scaffolds based on thermoplastic polyurethane, and doped with chondroitin sulfate and caseinophosphopeptides, able to mimic the structural, biomechanical, and biochemical functions of the TBI. The obtained scaffolds were characterized by a homogeneous microporous structure, and by a porosity optimal for cell nutrition and migration. They were also characterized by remarkable mechanical properties, reaching values comparable to the ones of the native tendons. The scaffolds promoted the tenocyte adhesion and proliferation when caseinophosphopetides and chondroitin sulfate are present in the 3D structure. In particular, caseinophosphopeptides' optimal concentration for cell proliferation resulted 2.4 mg/mL. Finally, the systems evaluation in vivo demonstrated the scaffolds' safety, since they did not cause any inflammatory effect nor foreign body response, representing interesting platforms for the regeneration of injured TBI., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Clay minerals are nanomaterials that have recently been recognized as enabling excipients that can promote cell adhesion, proliferation, and differentiation. When nanoclays are loaded in a 3D polymeric nanostructure, the cell-substrate interaction is enhanced, and other bioactive properties are optimized., Purpose: In this study, hectorite (HEC)- and montmorillonite (MMT)-doped polymeric scaffolds were explored for the treatment of deep and chronic skin lesions., Methods: Scaffolds were manufactured by means of electrospinning and then crosslinked by heating. Physicochemical analyses were correlated with in vitro biopharmaceutical characterization to predict the in vivo fate of the clay-doped scaffolds., Results and Discussion: The addition of MMT or HEC to the polymeric scaffold framework modifies the surface arrangement and, consequently, the potential of the scaffolds to interact with biological proteins. The presence of nanoclays alters the nanofiber morphology and size, and MMT doping increases wettability and protein adhesion. This has an impact on fibroblast behavior in a shorter time since scaffold stiffness facilitates cell adhesion and cell proliferation., Conclusion: MMT proved to perform better than HEC, and this could be related to its higher hydrophilicity and protein adhesion., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Miele et al.)

Background: Bone overgrowth after decompressive surgery for lumbar stenosis resulting in recurrence of neurological signs has not been reported in veterinary literature. However, there are few cases described in human medicine., Case Presentation: A 13-month-old entire female dog, a crossbreed between a Springer Spaniel and a Border Collie, weighing 24 kg, was referred with a 5-day history of progressive spastic paraplegia, indicative of a T3-L3 myelopathy. Magnetic resonance (MR) imaging revealed a right-sided L2-L3 compressive extradural lesion, compatible with epidural haemorrhage, which was confirmed by histopathology. The lesion was approached via right-sided L2-L3 hemilaminectomy and was successfully removed. One-year postoperatively the dog re-presented with pelvic limb ataxia. MR and computed tomography (CT) images demonstrated excessive vertebral bone formation affecting the right articular processes, ventral aspect of the spinous process of L2-L3, and contiguous vertebral laminae, causing spinal cord compression. Revision surgery was performed, and histopathology revealed normal or reactive osseous tissue with a possible chondroid metaplasia and endochondral ossification, failing to identify a definitive reason for the bone overgrowth. Nine-month postoperatively, imaging studies showed a similar vertebral overgrowth, resulting in minimal spinal cord compression. The patient remained stable with mild proprioceptive ataxia up until the last follow-up 18 months post-revision surgery., Conclusion: This is the first report in the veterinary literature of bone overgrowth after lumbar hemilaminectomy which resulted in neurological deficits and required a revision decompressive surgery., (© 2023. The Danish Veterinary Association.)

Introduction: Recently, mycelia of Ganoderma lucidum and Pleurotus ostreatus , edible fungi, have been characterized in vitro as self-growing biomaterials for tissue engineering since they are constituted of interconnected fibrous networks resembling the dermal collagen structure. Aim: This work aims to investigate the biopharmaceutical properties of G. lucidum and P. ostreatus mycelia to prove their safety and effectiveness in tissue engineering as dermal substitutes. Methods: The mycelial materials were characterized using a multidisciplinary approach, including physicochemical properties (morphology, thermal behavior, surface charge, and isoelectric point). Moreover, preclinical properties such as gene expression and in vitro wound healing assay have been evaluated using fibroblasts. Finally, these naturally-grown substrates were applied in vivo using a murine burn/excisional wound model. Conclusions: Both G. lucidum and P. ostreatus mycelia are biocompatible and able to safely and effectively enhance tissue repair in vivo in our preclinical model., Competing Interests: 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., (Copyright © 2023 Ruggeri, Miele, Contardi, Vigani, Boselli, Icaro Cornaglia, Rossi, Suarato, Athanassiou and Sandri.)

Quantifying human crystalline lens geometry as a function of age and accommodation is important for improved cataract and presbyopia treatments. In previous works we presented eigenlenses as a basis of 3-D functions to represent the full shape of the crystalline lens ex vivo . Also, we presented the application of eigenlenses to estimate the full shape of the lens in vivo from 3-D optical coherence tomography (OCT) images, where only the central part of the lens -visible through the pupil- is available. The current work presents a validation of the use of eigenlenses to estimate in vivo the full shape of dis-accommodated lenses. We used 14 ex vivo crystalline lenses from donor eyes (11-54 y/o) mounted in a lens stretcher, and measured the geometry and the power of the lenses using a combined OCT and ray tracing aberrometry system. Ex vivo , the full extent of the lens is accessible from OCT because the incident light is not blocked by the iris. We measured in non-stretched (fully accommodated) and stretched (mimicking in vivo dis-accommodated lenses) conditions. Then, we simulated computationally in vivo conditions on the obtained ex vivo lenses geometry (assuming that just the portion of the lens within a given pupil is available), and estimated the full shape using eigenlenses. The mean absolute error (MAE) between estimated and measured lens' diameters and volumes were MAE = 0.26 ± 0.18 mm and MAE = 7.0 ± 4.5 mm 3 , respectively. Furthermore, we concluded that the estimation error between measured and estimated lenses did not depend on the accommodative state (change in power due to stretching), and thus eigenlenses are also useful for the full shape estimation of in vivo dis-accommodated lenses., Competing Interests: EME (P), SM (P)., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Herein we developed a hydrogel based porous cross-linked scaffold intended for the treatment of chronic skin ulcers. It is made of collagen, the most abundant protein of mammals ECM, and chitosan, a natural polysaccharide endowed with numerous positive cues for wound repair. Different cross-linking methods, namely UV irradiation with the addition of glucose, addition of tannic acid as cross-linking agent and ultrasonication, were employed to prepare a cross-linked hydrogel with a highly interconnected 3D internal structure. The variables considered critical to obtain a suitable system for the envisaged application are the composition of hydrogels, especially the concentration of chitosan, and the concentration ratio between chitosan and collagen. Stable systems, characterized by high porosity, were obtained thanks to the use of freeze-drying process. To assess the influence of the above-mentioned variables on scaffold mechanical properties, a Design of Experiments (DoE) approach was exploited, which resulted in the identification of the best hydrogel composition. In vitro and in vivo assays on a fibroblast model cell line and on a murine model, respectively, demonstrated scaffold biocompatibility, biomimicry, and safety., Competing Interests: Declaration of competing interest 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., (Copyright © 2023. Published by Elsevier B.V.)

Periodontal regeneration is extremely limited and unpredictable due to structural complications, as it requires the simultaneous restoration of different tissues, including cementum, gingiva, bone, and periodontal ligament. In this work, spray-dried microparticles based on green materials (polysaccharides - gums - and a protein - silk fibroin) are proposed to be implanted in the periodontal pocket as 3D scaffolds during non-surgical treatments, to prevent the progression of periodontal disease and to promote the healing in mild periodontitis. Arabic or xanthan gum have been associated to silk fibroin, extracted from Bombyx mori cocoons, and loaded with lysozyme due to its antibacterial properties. The microparticles were prepared by spray-drying and cross-linked by water vapor annealing, inducing the amorphous to semi-crystalline transition of the protein component. The microparticles were characterized in terms of their chemico-physical features (SEM, size distribution, structural characterization - FTIR and SAXS, hydration and degradation properties) and preclinical properties (lysozyme release, antibacterial properties, mucoadhesion, in vitro cells adhesion and proliferation and in vivo safety on a murine incisional wound model). The encouraging preclinical results highlighted that these three-dimensional (3D) microparticles could provide a biocompatible platform able to prevent periodontitis progression and to promote the healing of soft tissues in mild periodontitis., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Acheta domesticus (house cricket) has been recently introduced into the official European list of novel foods, representing an alternative and sustainable food source. Up to now, the chemical characterization of this edible insect has been focused only on specific classes of compounds. Here, three production batches of an A. domesticus powder were investigated by means of a multimethodological approach based on NMR, FT-ICR MS, and GC-MS methodologies. The applied analytical protocol, proposed for the first time in the study of an edible insect, allowed us to identify and quantify compounds not previously reported in crickets. In particular, methyl-branched hydrocarbons, previously identified in other insects, together with other compounds such as citrulline, formate, γ -terpinene, p -cymene, α -thujene, β -thujene, and 4-carene were detected. Amino acids, organic acids, and fatty acids were also identified and quantified. The improved knowledge of the chemical profile of this novel food opens new horizons both for the use of crickets as a food ingredient and for the use of extracts for the production of new formulations. In order to achieve this objective, studies regarding safety, biological activity, bioaccessibility, and bioavailability are needed as future perspectives in this field.

Tendon disorders are common medical conditions, which can be greatly debilitating as they are often accompanied by great pain and inflammation. The techniques used nowadays for the treatment of chronic tendon injuries often involve surgery. However, one critical aspect of this procedure involves the scar tissue, characterized by mechanical properties that vary from healthy tissue, rendering the tendons inclined to reinjury or rupture. Synthetic polymers, such as thermoplastic polyurethane, are of special interest in the tissue engineering field as they allow the production of scaffolds with controlled elastic and mechanical properties, which could guarantee an effective support during the new tissue formation. The aim of this work was the design and the development of tubular nanofibrous scaffolds based on thermoplastic polyurethane and enriched with cerium oxide nanoparticles and chondroitin sulfate. The scaffolds were characterized by remarkable mechanical properties, especially when tubular aligned, reaching values comparable to the ones of the native tendons. A weight loss test was performed, suggesting a degradation in prolonged times. In particular, the scaffolds maintained their morphology and also remarkable mechanical properties after 12 weeks of degradation. The scaffolds promoted the cell adhesion and proliferation, in particular when in aligned conformation. Finally, the systems in vivo did not cause any inflammatory effect, representing interesting platforms for the regeneration of injured tendons.

Several nanomedicine based medicinal products recently reached the market thanks to the drive of the COVID-19 pandemic. These products are characterized by criticality in scalability and reproducibility of the batches, and the manufacturing processes are now being pushed towards continuous production to face these challenges. Although the pharmaceutical industry, because of its deep regulation, is characterized by slow adoption of new technologies, recently, the European Medicines Agency (EMA) took the lead in pushing for process improvements using technologies already established in other manufacturing sectors. Foremost among these technologies, robotics is a technological driver, and its implementation in the pharma field should cause a big change, probably within the next 5 years. This paper aims at describing the regulation changes mainly in aseptic manufacturing and the use of robotics in the pharmaceutical environment to fulfill GMP (good manufacturing practice). Special attention is therefore paid at first to the regulatory aspect, explaining the reasons behind the current changes, and then to the use of robotics that will characterize the future of manufacturing especially in aseptic environments, moving from a clear overview of robotics to the use of automated systems to design more efficient processes, with reduced risk of contamination. This review should clarify the regulation and technological scenario and provide pharmaceutical technologists with basic knowledge in robotics and automation, as well as engineers with regulatory knowledge to define a common background and language, and enable the cultural shift of the pharmaceutical industry.

The mechanics of accommodation is a complex process that involves multiple intraocular ocular structures. Recent studies suggest that there is deformation of the sclera during accommodation that may also play a role in accommodation, influencing ciliary muscle contraction and contributing to the accommodative response. However, the type and magnitude of the deformations measured varies significantly across studies. We present high-resolution synchronous OCT measurements of the anterior sclera contour and thickness and lens thickness acquired in real-time during accommodative responses to 4D step stimuli. The lens thickness was used as an assessment of objective accommodation. No changes in nasal and temporal anterior scleral contour and scleral thickness were found during accommodation within the precision of our measurements. Our results demonstrate that there are no significant scleral deformations during accommodation., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Clay minerals are historically among the most used materials with a wide variety of applications. In pharmaceutical and biomedical fields, their healing properties have always been known and used in pelotherapy and therefore attractive for their potential. In recent decades, the research has therefore focused on the systematic investigation of these properties. This review aims to describe the most relevant and recent uses of clays in the pharmaceutical and biomedical field, especially for drug delivery and tissue engineering purposes. Clay minerals, which are biocompatible and non-toxic materials, can act as carriers for active ingredients while controlling their release and increasing their bioavailability. Moreover, the combination of clays and polymers is useful as it can improve the mechanical and thermal properties of polymers, as well as induce cell adhesion and proliferation. Different types of clays, both of natural (such as montmorillonite and halloysite) and synthetic origin (layered double hydroxides and zeolites), were considered in order to compare them and to assess their advantages and different uses.

Acute Kidney Injury (AKI) is associated with a great increase in morbidity and mortality in severely burned patients and occurs as a complication in more than 25% of these cases. The onset of ARF may be early or late. Early AKI depends mainly on reduced cardiac output resulting from fluid loss, rhabdomyolysis, or hemolysis. Late AKI, instead, is usually a consequence of sepsis and is often associated with multiorgan failure (MOF). The first sign of AKI is the contraction of diuresis despite adequate volemic filling, which is followed by elevation of serum urea and creatinine. Fluid therapy is the main treatment in the burned victim: in the first few hours after injury, it aims to avoid hypovolemic shock and the possible related MOF, while later it becomes the cornerstone of treatment, besides antibiotic therapy in the case of sepsis onset. Particular care must also be taken in the choice of administered drugs in order to avoid possible nephrotoxic damage in addition to burning injury. Hemodialytic renal replacement therapy is used both for water balance management in patients requiring massive fluid infusions and for blood purification purposes to control the metabolic state, acid-base balance, and electrolytes abnormality. Our team has been collaborating for over 25 years in the management of severely burned patients admitted to the Centro Grandi Ustionati at the Bufalini Hospital in Cesena., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Bentonite or palygorskite-based hydrogels have recently been suggested as a strategy to increase bioavailability and control the retention and release of therapeutic candidates. In this work, clay-based hydrogels loaded with diclofenac acid nanocrystals have been successfully designed and developed. The aim was to improve diclofenac solubility, its dissolution rate and to enhance its local bioavailability after topical application. For this purpose, diclofenac acid nanocrystals were prepared by wet media milling technology and then loaded into inorganic hydrogels based on bentonite and/or palygorskite. Diclofenac acid nanocrystals were characterized by morphology, size, and zeta potential. Moreover, rheological behavior, morphology, solid state, release studies, and in vitro skin penetration/permeation of diclofenac acid nanocrystals-loaded hydrogels were performed. The hydrogels were characterized by a crystalline structure, and demonstrated that the inclusion of diclofenac in clay-based hydrogels resulted in an increased thermal stability. The presence of both palygorskite and bentonite reduced nanocrystal mobility, and consequently its release and penetration into the skin. On the other hand, bentonite- or palygorskite-based hydrogels revealed great potential as an alternative strategy to enhance topical bioavailability of DCF nanocrystals, enhancing their penetration to the deeper skin layers.

Peripheral nerve injury is one of the most debilitating pathologies that severely impair patients' life. Although many efforts have been made to advance in the treatment of such a complex disorder, successful strategies to ensure full recovery are still scarce. The aim of the present work was to develop flexible and mechanically resistant platforms intended to act as a support and guide for neural cells during the regeneration process of peripheral nerve injury. For this purpose, poly(lactic- co -glycolic acid) (PLGA)/poly(d,l-lactic acid) (PDLLA)/poly(ethylene glycol) 400 (PEG)-multichannel-based scaffolds (MCs) were prepared through a multistep process involving electrospun microfibers coated with a polymer blend solution and used as a sacrificial mold. In particular, scaffolds characterized by random (MCR) and aligned (MCA) multichannel were obtained. A design of experiments approach (DoE) was employed to identify a scaffold-optimized composition. MCs were characterized for morphological and mechanical properties, suturability, degradability, cell colonization, and in vivo safety. A new biodegradable, biocompatible, and safe microscale multichannel scaffold was developed as the result of an easy multistep procedure.

Background: Incorporating real-world data in the drug development process allows the improvement of health outcomes by providing better representation of actual patterns of drug safety and efficacy., Aims and Methods: Here, we present the results of a retroprospective, observational real-life study of 154 patients with myelofibrosis treated with ruxolitinib in a real-life setting in seven Italian centers of the MYNERVA project., Results: Median drug exposure was 29 (range, 3-98) months. Discontinuation rate was 27% after a median time of 13 (range, 3-61). While hematological toxicities were in line with previous findings, infections occurred frequently, representing a not negligible cause of discontinuation and death. Anemia, symptoms, and spleen responses were obtained at any time in 23%, 91%, and 68% of patients, respectively; most patients achieved their responses by week 24. Larger splenomegaly and delayed treatment initiation correlated with lower spleen response at 24 weeks. Spleen response was associated with a superior overall survival, regardless of DIPSS. Of interest, both achievement and loss of spleen response had prognostic implications., Discussion and Conclusion: Overall, our findings provide insights on the efficacy and safety of ruxolitinib in a real-world, multicenter cohort of Italian MF patients., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Blood-brain barrier (BBB) permeability can be assessed quantitatively using advanced imaging analysis., Hypothesis/objectives: Quantification and characterization of blood-brain barrier dysfunction (BBBD) patterns in dogs with brain tumors can provide useful information about tumor biology and assist in distinguishing between gliomas and meningiomas., Animals: Seventy-eight hospitalized dogs with brain tumors and 12 control dogs without brain tumors., Methods: In a 2-arm study, images from a prospective dynamic contrast-enhanced (DCE; n = 15) and a retrospective archived magnetic resonance imaging study (n = 63) were analyzed by DCE and subtraction enhancement analysis (SEA) to quantify BBB permeability in affected dogs relative to control dogs (n = 6 in each arm). For the SEA method, 2 ranges of postcontrast intensity differences, that is, high (HR) and low (LR), were evaluated as possible representations of 2 classes of BBB leakage. BBB score was calculated for each dog and was associated with clinical characteristics and tumor location and class. Permeability maps were generated, using the slope values (DCE) or intensity difference (SEA) of each voxel, and analyzed., Results: Distinctive patterns and distributions of BBBD were identified for intra- and extra-axial tumors. At a cutoff of 0.1, LR/HR BBB score ratio yielded a sensitivity of 80% and specificity of 100% in differentiating gliomas from meningiomas., Conclusions and Clinical Importance: Blood-brain barrier dysfunction quantification using advanced imaging analyses has the potential to be used for assessment of brain tumor characteristics and behavior and, particularly, to help differentiating gliomas from meningiomas., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Fostamatinib, a spleen tyrosine kinase (Syk) inhibitor, represents a new therapeutic opportunity for patients with immune thrombocytopenia (ITP) in Europe and Italy. However, the positioning of this drug in patient's therapeutic sequence is undefined within the most recent international guidelines. The conclusions from a consensus meeting between Italian experts, whose task was to outline the profile of the ideal candidate to receive fostamatinib, are reported here. A modified Delphi methodology was used to achieve shared statements, which were reported in a narrative form. In particular, the panelists examined the strengths and weaknesses of the registration studies in terms of clinical outcomes, the safety profile of fostamatinib, the drug's impact on the quality of life of patients with chronic ITP, and the potential benefits of its use in the pandemic era. Although the experience with thrombopoietin receptor agonists (TPO-RAs) and the amount of data from real-world studies suggest the preferential use of these drugs as a second-line treatment in most patients, the absence of an increased thrombotic risk in the clinical trials could make fostamatinib a reasonable choice in patients with an increased risk of vascular events. An unstable platelet count during TPO-RAs might also justify a switch to the Syk inhibitor, which is more likely to stabilize the platelet count in responders. Fostamatinib may be preferred to immunosuppressors during the SARS-CoV-2 pandemic, in patients at infectious risk, or in case of contraindication to splenectomy. Finally, the novel mechanism of action makes it an attractive drug in multi-refractory patient., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AL has consulted for and participated on speakers’ bureaus for Amgen, Grifols, Novartis, Sobi. BF received consultancy honoraria from Amgen, Janssen, Momenta, Novartis, and Sobi. VDS received advisory board and speaker fees from Amgen, Grifols, Sobi, and Novartis. SS received consultancy honoraria from Amgen, CSL, Janssen, Novartis, Novo Nordisk, Pfizer, Sobi, and Takeda. NV received advisory board and speaker fees from Amgen, Grifols, and Novartis. FZ received advisory board and speaker fees from Amgen, Argenx, Grifols, Novartis and Sobi; funding for clinical studies from, Amgen, Grifols, Novartis, Sobi. FR received advisory board/speakers’ bureau fees from Amgen, Argenx, and Novartis. Grifols invited the expert panel in an advisory board and facilitated discussion but did not fund or take part to Delphi process, writing or revising the manuscript., (© The Author(s), 2023.)

Tendon disorders are common medical conditions that could lead to significant disability, pain, healthcare costs, and a loss of productivity. Traditional approaches require long periods of treatment, and they largely fail due to the tissues weakening and the postoperative alterations of the normal joint mechanics. To overcome these limitations, innovative strategies for the treatment of these injuries need to be explored. The aim of the present work was the design of nano-fibrous scaffolds based on poly(butyl cyanoacrylate) (PBCA), a well-known biodegradable and biocompatible synthetic polymer, doped with copper oxide nanoparticles and caseinphosphopeptides (CPP), able to mimic the hierarchical structure of the tendon and to improve the tissue healing potential. These were developed as implants to be sutured to reconstruct the tendons and the ligaments during surgery. PBCA was synthetized, and then electrospun to produce aligned nanofibers. The obtained scaffolds were characterized for their structure and physico-chemical and mechanical properties, highlighting that CuO and CPP loading, and the aligned conformation determined an increase in the scaffold mechanical performance. Furthermore, the scaffolds loaded with CuO showed antioxidant and anti-inflammatory properties. Moreover, human tenocytes adhesion and proliferation to the scaffolds were assessed in vitro. Finally, the antibacterial activity of the scaffolds was evaluated using Escherichia coli and Staphylococcus aureus as representative of Gram-negative and Gram-positive bacteria, respectively, demonstrating that the CuO-doped scaffolds possessed a significant antimicrobial effect against E. coli . In conclusion, scaffolds based on PBCA and doped with CuO and CPP deserve particular attention as enhancers of the tendon tissue regeneration and able to avoid bacterial adhesion. Further investigation on the scaffold efficacy in vivo will assess their capability for enhancing the tendon ECM restoration in view of accelerating their translation to the clinic.

Purpose: To determine whether lens mechanical dynamics change with age and with accommodative demands., Methods: Lens thickness microfluctuations were measured using a high-speed custom-built spectral domain optical coherence tomography system in five young adults (20 to 25 years old) at 0 diopters (D), 2 D, 4 D, and maximum accommodative demand and in five prepresbyopes (38 to 45 years old) under relaxed and maximal accommodation. For each state, the measurements were repeated four times during the same session. Images of the central 2-mm zone of the lens comprising 170 A-lines/frame were acquired for 10 seconds, and axial lens thickness change was measured. Lens thickness microfluctuations (µm²/Hz) were assessed by integrating the power spectrum of lens thickness microfluctuations between 0 and 4 Hz., Results: The amplitude of lens microfluctuations was higher in the accommodated states than in the relaxed state in both age groups. Lens microfluctuations were higher in young adult participants than in prepresbyopes, with a significant difference in relaxed and maximally accommodated states (P = 0.04 and P = 0.04). In the young participants, the amplitude of microfluctuations reached a plateau at maximum accommodation., Conclusions: Lens mechanical dynamics are both age and accommodation dependent. The decrease in lens thickness microfluctuations with age is consistent with an age-related increase in lens stiffness or decrease of the ciliary muscle displacement. The lens does not contribute to the high-frequency component of ocular dioptric microfluctuations.

Quantifying the full 3-D shape of the human crystalline lens is important for improving intraocular lens power or sizing calculations in treatments of cataract and presbyopia. In a previous work we described a novel method for the representation of the full shape of the ex vivo crystalline lens called eigenlenses , which proved more compact and accurate than compared state-of-the art methods of crystalline lens shape quantification. Here we demonstrate the use of eigenlenses to estimate the full shape of the crystalline lens in vivo from optical coherence tomography images, where only the information visible through the pupil is available. We compare the performance of eigenlenses with previous methods of full crystalline lens shape estimation, and demonstrate an improvement in repeatability, robustness and use of computational resources. We found that eigenlenses can be used to describe efficiently the crystalline lens full shape changes with accommodation and refractive error., Competing Interests: EME (P), SM (P)., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Insects, especially crickets, have been proposed as a novel source of nutrients in human nutrition since they possess bioactive molecules, including high protein content, lipids, chitin, vitamins and minerals. In this work, the nutritional and functional properties of a novel Italian spray-dried (SD) cricket powder were evaluated. The powder was characterized by physico-chemical properties (morphology, size distribution, solid state, thermal profiles, and surface zeta potential), and antioxidant properties. Moreover, preclinical properties (cytocompatibility and pro-inflammatory immune response) were assessed. The powder was characterized by microparticle structure with bulges and rough surfaces, showing distinctive antioxidant properties. The preclinical results suggested that the SD crickets were biocompatible towards Caco-2 and macrophages without immune response, representing an interesting material for the food industry that could provide health benefits in addition to the basic nutritional value of traditional foods.

The poor water solubility of a significant number of active pharmaceutical ingredients (API) remains one of the main challenges in the drug development process, causing low bioavailability and therapeutic failure of drug candidates. Curcumin is a well-known Biopharmaceutics Classification System (BCS) class IV drug, characterized by lipophilicity and low permeability, which hampers topical bioavailability. Given these premises, the aim of this work was the design and the development of curcumin nanocrystals and their incorporation into natural inorganic hydrogels for topical application. Curcumin nanocrystals were manufactured by the wet ball milling technique and then loaded in clay-based hydrogels. Bentonite and/or palygorskite were selected as the inorganic gelling agents. Curcumin nanocrystal-loaded hydrogels were manufactured by means of a homogenization process and characterized with respect to their chemico-physical properties, in vitro release, antioxidant activity and skin permeation. The results highlighted that the presence of bentonite provided an increase of curcumin skin penetration and simultaneously allowed its radical scavenging properties, due to the desirable rheological characteristics, which should guarantee the necessary contact time of the gel with the skin.

Objective: To evaluate the efficiency and safety of a doramectin-based treatment protocol in dogs affected by intraspinal spirocercosis (Spirocerca lupi)., Animals: Client-owned dogs that were admitted to a veterinary hospital during 2021 to 2022 with acute onset of neurological signs and diagnosed with intraspinal spirocercosis. All dogs underwent complete neurological evaluation, CSF analysis, PCR confirmation of CNS S lupi infection, and follow-up evaluation of at least 6 months., Procedures: Upon diagnosis, dogs were treated with doramectin at a dose of 400 μg/kg, SC, q 24 h for 3 consecutive days, followed by the same dose once a week for 6 weeks. Prednisone was administered at a dose of 1 mg/kg, PO, q 24 h and tapered every 3 days. Antimicrobial clindamycin was administered at a dose of 12.5 mg/kg, PO, q 12 h for 7 days to reduce the risk of secondary spinal cord infection. Short- and long-term outcomes (1 week to 56 months) were recorded., Results: 8 dogs fulfilled the inclusion criteria, 7 of which presented with neurological deficits and 1 with cervical pain. Initiation of treatment was associated with stopping the deterioration in 7 of 8 dogs. Seven dogs improved and 6 recovered ambulation. One dog was euthanized due to lack of improvement. Six of the recovered dogs were still ataxic on the last follow-up examination at 6 to 56 months. No adverse effects of the drug were noted., Clinical Relevance: Frequent administration of doramectin was found to be safe and effective in preventing neurological deterioration in dogs with intraspinal spirocercosis.

A multicenter retrospective study was designed to assess clinical outcome of COVID-19 in patients with hematological malignancies (HM) following treatment with anti-SARS-CoV-2 convalescent plasma (CP) or standard of care therapy. To this aim, a propensity score matching was used to assess the role of non-randomized administration of CP in this high-risk cohort of patients from the Italian Hematology Alliance on COVID-19 (ITA-HEMA-COV) project, now including 2049 untreated control patients. We investigated 30- and 90-day mortality, rate of admission to intensive care unit, proportion of patients requiring mechanical ventilatory support, hospitalization time, and SARS-CoV-2 clearance in 79 CP recipients and compared results with 158 propensity score-matched controls. Results indicated a lack of efficacy of CP in the study group compared with the untreated group, thus confirming the negative results obtained from randomized studies in immunocompetent individuals with COVID-19. In conclusion, this retrospective analysis did not meet the primary and secondary end points in any category of immunocompromized patients affected by HM., (© 2022 John Wiley & Sons Ltd.)

The introduction of new therapeutic agents for multiple myeloma (MM), including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, has improved the outcomes of patients but, in parallel, has changed the frequency and epidemiology of thrombotic events. Thrombosis is now a significant cause of morbidity and mortality in MM patients, and optimal thromboprophylaxis is far from being reached. Moving from the recognition that the above issue represents an unmet clinical need, an expert panel assessed the scientific literature and composed a framework of recommendations for improving thrombosis control in patients who are candidates for active treatment for MM. The panel generated key clinical questions using the criterion of clinical relevance through a Delphi process. It explored four domains, i.e., thrombotic risk factors and risk stratification, primary thromboprophylaxis, management of acute thrombotic events, and secondary thromboprophylaxis. The recommendations issued may assist hematologists in minimizing the risk of thrombosis and guarantee adherence to treatment in patients with MM who are candidates for active treatment.

Patients with Philadelphia-negative myeloproliferative neoplasms are at high risk of thrombotic events (TEs). Predisposing factors have been identified in essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (primary MF, PMF), while yet not recognized in post PV/ET-MF (known as secondary MF, SMF). Within the 1258 SMF of the MYSEC (MYelofibrosis SECondary to PV and ET) dataset, 135 (10.7%) developed a TE at a median follow-up of 3.5 years (range, 1-21.4), with an incidence of 2.3% patients per year. Venous events accounted for two-thirds of the total. Cox multivariable analysis, supported by Fine-Gray models with death as competitive risk, showed that being on cytoreductive therapy at time of SMF evolution is associated with an absolute risk reduction of thrombosis equal to 3.3% within 3 years. Considering individually cytoreductive therapies, univariate regression model found that both conventional cytoreduction, mainly hydroxyurea, (HR 0.41, 95% CI: 0.26-0.65, p = 0.0001) and JAK inhibitors, mostly ruxolitinib, (HR 0.50, 95% CI: 0.24-1.02, p = 0.05) were associated with fewer thrombosis. Our study informs treating physicians of a non-low incidence of TEs in post PV/ET-MF and of the potential protective role of cytoreductive therapy in terms of thrombotic events., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The transition toward more sustainable food systems, which already represents a central element of the European Farm to Fork and Green Deal strategies, could be an effective measure to contribute to global decarbonization and greenhouse gas (GHGs) reduction goals; concurrently, it could improve the health status and nutrition of the global population. In this context, the Mediterranean diet (MD) could play a considerable role, as it is generally recognized as a more balanced, healthy, and sustainable eating pattern than Western consumption patterns, which are characterized by excess food and high energy content, thus causing undesirable effects on both human health and the environment. Although traditionally linked to MD, Italy sees relatively moderate adherence by its citizens, as they consume about +75% of the daily caloric intake recommended by MD. Therefore, this study aims to quantitatively assess the potential environmental, economic, and health impacts of this lower adherence to MD by Italians. Current Italian Food Patterns (CIFP) in 2019 were analyzed and compared to the MD recommended amounts through a Life Cycle Thinking (LCT) approach (LCA) and carbon footprint (CF) analysis. The results show that CIFP, compared to MD, has +133% greater impacts on the environmental macro-area, +100% greater impacts on the human health macro-area, and +59% greater impacts on the economic macro-area (with annual fossil and mineral resource savings of $53.35 per person, $3.2 billion per year). The analysis also shows that CIFP has a CF of 6.54 × 10 1 kg CO 2 eq, +142% over MD (2.7 × 10 1 kg CO 2 eq), resulting in a lower environmental impact of the Mediterranean diet.

Chronic wounds (resulting from underlying disease, metabolic disorders, infections, trauma, and even tumours) pose significant health problems. In this work, microparticles, based on polysaccharides (maltodextrin or dextran) and amino acids, and doped with antibacterial nanoparticles (CuO or ZnO NPs) are designed. Smart nano-in-microparticles with a hierarchical 3D structure are developed. The ultimate goal aims at an innovative platform to achieve skin repair and to manage skin colonization by avoiding infection that could delay and even impair the healing process. The microparticles are prepared by spray-drying and cross-linked by heating, to obtain insoluble scaffolds able to facilitate cell proliferation in the wound bed. The nano-in-microparticles are characterized using a multidisciplinary approach: chemico-physical properties (SEM, SEM-EDX, size distribution, swelling and degradation properties, structural characterization - FTIR, XRPD, SAXS - mechanical properties, surface zeta potential) and preclinical properties (in vitro biocompatibility and whole-blood clotting properties, release studies and antimicrobial properties, and in vivo safety and efficacy on murine burn/excisional wound model) were assessed. The hierarchical 3D nano-in microparticles demonstrate to promote skin tissue repair in a preclinical study, indicating that this platform deserves particular attention and further investigation will promote the prototypes translation to clinics., Competing Interests: 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., (© 2022 The Authors.)

Background: Glioblastoma is the most aggressive form of brain cancer, characterised by high proliferation rates and cell invasiveness. Despite advances in surgery and radio-chemotherapy, patients continue to have poor prognoses, with a survival rate of 14-15 months. Thus, new therapeutic strategies are needed. Non-ionising electromagnetic fields represent an emerging option given the potential advantages of safety, low toxicity and the possibility to be combined with other therapies., Methods: Here, the anticancer activity of quantum molecular resonance (QMR) was investigated. For this purpose, three glioblastoma cell lines were tested, and the QMR effect was evaluated on cancer cell proliferation rate and aggressiveness. To clarify the QMR mechanism of action, the proteomic asset after stimulation was delineated. Mesenchymal stromal cells and astrocytes were used as healthy controls., Results: QMR affected cancer cell proliferation, inducing a significant arrest of cell cycle progression and reducing cancer tumorigenicity. These parameters were not altered in healthy control cells. Proteomic analysis suggested that QMR acts not only on DNA replication but also on the machinery involved in the mitotic spindle assembly and chromosome segregation. Moreover, in a combined therapy assessment, QMR significantly enhanced temozolomide efficacy., Conclusions: QMR technology appears to be a promising tool for glioblastoma treatment., (© 2022. The Author(s).)

Purpose: To determine whether patient-customized paraxial eye models that do not rely on exact ray tracing and do not consider aberrations can accurately predict pseudophakic refraction., Setting: Bascom Palmer Eye Institute, Miami, Florida., Design: Prospective study., Methods: Cataract surgery patients with and without a history of refractive surgery were included. Manifest refraction, corneal biometry, and extended-depth optical coherence tomography (OCT) imaging were performed at least 1 month postoperatively. Corneal and OCT biometry were used to create paraxial eye models. The pseudophakic refraction simulated using the eye model was compared with measured refraction to calculate prediction error., Results: 49 eyes of 33 patients were analyzed, of which 12 eyes from 9 patients had previous refractive surgery. In eyes without a history of refractive surgery, the mean prediction error was 0.08 ± 0.33 diopters (D), ranging from -0.56 to 0.79 D, and the mean absolute error was 0.27 ± 0.21 D. 31 eyes were within ±0.5 D, and 36 eyes were within ±0.75 D. In eyes with previous refractive surgery, the mean prediction error was -0.44 ± 0.58 D, ranging from -1.42 to 0.32 D, and the mean absolute error was 0.56 ± 0.46 D. 7 of 12 eyes were within ±0.5 D, 8 within ±0.75 D, and 10 within ±1 D. All eyes were within ±1.5 D., Conclusions: Accurate calculation of refraction in postcataract surgery patients can be performed using paraxial optics. Measurement uncertainties in ocular biometry are a primary source of residual prediction error., (Copyright © 2022 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Quantifying shape changes in the ciliary muscle during accommodation is essential in understanding the potential role of the ciliary muscle in presbyopia. The ciliary muscle can be imaged in-vivo using OCT but quantifying the ciliary muscle shape from these images has been challenging both due to the low contrast of the images at the apex of the ciliary muscle and the tedious work of segmenting the ciliary muscle shape. We present an automatic-segmentation tool for OCT images of the ciliary muscle using fully convolutional networks. A study using a dataset of 1,039 images shows that the trained fully convolutional network can successfully segment ciliary muscle images and quantify ciliary muscle thickness changes during accommodation. The study also shows that EfficientNet outperforms other current backbones of the literature., Competing Interests: The authors declare no conflicts of interest., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by enhanced platelet production and thrombotic complications. The inhibition of platelet cyclooxygenase (COX) activity by the standard once-daily aspirin is mostly incomplete due to accelerated thrombopoiesis. The phase II Aspirin Regimens in EsSential thrombocythemia (ARES) trial has recently compared the efficacy of once- vs. twice- or three-times daily low-dose aspirin in inhibiting platelet thromboxane (TX) A 2 production, as reflected by serum (s) TXB 2 measurements. The present substudy characterized the determinants of the highly variable response to the standard aspirin 100 mg once-daily regimen in fully compliant patients with ET and the effects of the experimental dosing regimens on response variability. By multivariable analysis, the platelet count (directly) and cytoreductive treatment (inversely) were significantly associated with sTXB 2 values in 218 patients with ET. However, the platelet count positively correlated with sTXB 2 in patients not being treated with cytoreductive drugs (ρ = 0.51, P < 0.01, n = 84), but not in patients on cytoreduction. Patients in the lowest sTXB 2 quartile were older, more often on cytoreductive drugs, had lower platelet count and Janus-Associated Kinase2 (JAK2)-V617F allele frequency as compared with patients in the upper sTXB 2 quartiles. After 2 weeks of a twice- or 3-times daily aspirin regimen, the association between the platelet count and sTXB 2 became similar in cytoreduced and non-cytoreduced patients. In conclusion, the platelet count appears the strongest determinant of TXA 2 inhibition by once-daily low-dose aspirin in ET, with different patterns depending of cytoreductive treatment. More frequent aspirin dosing restores adequate platelet inhibition and reduces interindividual variability, independently of cytoreduction., (© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: The blood-brain barrier (BBB), which separates the intravascular and neuropil compartments, characterizes the vascular bed of the brain and is essential for its proper function. Recent advances in imaging techniques have driven the development of methods for quantitative assessment of BBB permeability., Hypothesis/objectives: Permeability of the BBB can be assessed quantitatively in dogs with meningoencephalitis of unknown origin (MUO) and its status is associated with the occurrence of seizures., Animals: Forty dogs with MUO and 12 dogs without MUO., Methods: Retrospective, prospective cohort study. Both dynamic contrast enhancement (DCE) and subtraction enhancement analysis (SEA) methods were used to evaluate of BBB permeability in affected (DCE, n = 8; SEA, n = 32) and control dogs (DCE, n = 6; SEA, n = 6). Association between BBB dysfunction (BBBD) score and clinical characteristics was examined. In brain regions where BBBD was identified by DCE or SEA magnetic resonance imaging (MRI) analysis, immunofluorescent staining for albumin, glial fibrillary acidic protein, ionized calcium binding adaptor molecule, and phosphorylated mothers against decapentaplegic homolog 2 were performed to detect albumin extravasation, reactive astrocytes, activated microglia, and transforming growth factor beta signaling, respectively., Results: Dogs with BBBD had significantly higher seizure prevalence (72% vs 19%; P = .01) when compared to MUO dogs with no BBBD. The addition of SEA to routine MRI evaluation increased the identification rate of brain pathology in dogs with MUO from 50% to 72%., Conclusions and Clinical Importance: Imaging-based assessment of BBB integrity has the potential to predict risk of seizures in dogs with MUO., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)