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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.)

Background: Cataract waiting lists are growing globally. Pragmatic, cost-effective methods are required to prioritise the most urgent cases. Here we investigate the feasibility of using a third-party pen-and-paper contrast sensitivity, CS, test (SpotChecks TM ), delivered by mail, and performed by patients at home unsupervised, to flag eyes requiring surgery., Methods: Pen-and-paper CS tests were mailed to 233 people waiting for a cataract assessment, along with a prepaid return envelope (cross-sectional study). Response rates were tabulated (stratified by age, sex and socioeconomic status), and test scores analysed to see how well the home tests predicted which eyes were listed subsequently for surgery. A subset of patients (N = 39) also underwent in-person follow-up testing, to confirm the accuracy of the home data., Results: Forty-six percent of patients responded (216 eyes). No gross differences were observed between respondents and non-respondents, either in terms of age, sex, socioeconomic status, or geographic location (all P > 0.05). The home-test CS scores predicted which eyes were subsequently listed for surgery, with an AUROC {±CI 95% } of 0.69 {0.61-0.76}. Predictive performance was further-improved when machine learning was used to combine CS scores with letter acuity, extracted from patients' medical records (AUROC {±CI 95% } = 0.77 {0.70-0.83}). Among 39 patients who underwent follow-up testing, home CS scores were correlated with various measures made in clinic: biometry signal-to-noise (P = 0.032), LogMAR acuity, Pelli-Robson CS and SpotChecks CS (all P < 0.001)., Conclusions: Mailing patients pen-and-paper CS tests may be a feasible, 'low-tech' way of prioritising patients on cataract waiting lists., (© 2024. The Author(s).)

Carbon nitride compounds (CNCs) in the form of graphitic carbon nitride (g-C 3 N 4 ) and poly(heptazine imide) were synthesized using different metal chloride salts (MCl x ), i. e., NaCl, KCl and CaCl 2 , as sacrificial templates and by varying the MCl x to melamine molar ratios. A systematic study of their photocatalytic activity for H 2 production in relation to the physicochemical, morphological, and optical properties was carried out. Each sample was tested achieving the highest hydrogen evolution rates of about 7660 μmol g -1  h -1 , 5380 μmol g -1  h -1 and 3140 μmol g -1  h -1 using CaCl 2 , KCl, and NaCl, respectively. This work demonstrates how the synthesis of CNCs with different MCl x leads to the production of high-performance photocatalysts due to a combination of factors as the formation of vacancies or cyano groups, a shift in the optical threshold and tuning of micro(nano)structure. The results demonstrate that, when CaCl 2 is used as a sacrificial template, porous and exfoliated g-C 3 N 4 nanosheets are formed leading to hydrogen productions which outperform most of the previously reported g-C 3 N 4 prepared using a single synthetic step., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

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.

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.)

We report Atacama Large Millimeter/submillimeter Array (ALMA) high-angular resolution (∼50 au) observations of the binary system SVS13-A. More specifically, we analyse deuterated water (HDO) and sulfur dioxide (SO 2 ) emission. The molecular emission is associated with both the components of the binary system, VLA4A and VLA4B. The spatial distribution is compared to that of formamide (NH 2 CHO), previously analysed in the system. Deuterated water shows an additional emitting component spatially coincident with the dust-accretion streamer, at a distance ≥120 au from the protostars, and at blue-shifted velocities (>3 km s -1 from the systemic velocities). We investigate the origin of the molecular emission in the streamer, in light of thermal sublimation temperatures calculated using updated binding energy (BE) distributions. We propose that the observed emission is produced by an accretion shock at the interface between the accretion streamer and the disk of VLA4A. Thermal desorption is not completely excluded in case the source is actively experiencing an accretion burst.

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.

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.

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.

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.

Background/aims: To review the clinicopathological features of caruncle biopsies carried out at a district general hospital in the United Kingdom (UK), and compare with other centres where data has been published., Methods: Retrospective, single-centre, observational case series between 2004-2020., Results: A total of 31 lesions from 31 patients were analysed. 18 of 31 patients were men (58%), and the age ranged from 12 to 91 years. 13 different histopathological types of lesions were identified in our case series, including 9 melanocytic nevi (29%), 7 benign squamous papillomas (23%), 5 skin adnexal lesions (16%), 3 chronic inflammation (10%), 3 epithelial cysts (10%), 1 basal cell carcinoma (3%), 2 malignant melanomas (6%) and l lymphoproliferative disorder (3%). Pre-operative suspected diagnoses were often vague but correct in 12 of 18 cases (67%), where data was available., Conclusion: The uncommon nature and variety of caruncular lesions make the diagnostic process difficult. Our case series is the first reported in the UK, showing a slightly higher proportion of malignant melanomas, in keeping with the population demographics. Excisional biopsies would, therefore, be prudent in the majority of cases to rule out any possible malignancy.

The enthesis is an extremely specific region, localized at the tendon-bone interface (TBI) and made of a hybrid connection of fibrocartilage with minerals. The direct type of enthesis tissue is commonly subjected to full laceration, due to the stiffness gradient between the soft tissues and hard bone, and this often reoccurs after surgical reconstruction. For this purpose, the present work aimed to design and develop a tubular scaffold based on pullulan (PU) and chitosan (CH) and intended to enhance enthesis repair. The scaffold was designed with a topographical gradient of nanofibers, from random to aligned, and hydroxyapatite (HAP) nanoparticles along the tubular length. In particular, one part of the tubular scaffold was characterized by a structure similar to bone hard tissue, with a random mineralized fiber arrangement; while the other part was characterized by aligned fibers, without HAP doping. The tubular shape of the scaffold was also designed to be extemporarily loaded with chondroitin sulfate (CS), a glycosaminoglycan effective in wound healing, before the surgery. Micro CT analysis revealed that the scaffold was characterized by a continuous gradient, without interruptions from one end to the other. The gradient of the fiber arrangement was observed using SEM analysis, and it was still possible to observe the gradient when the scaffold had been hydrated for 6 days. In vitro studies demonstrated that human adipose stem cells (hASC) were able to grow and differentiate onto the scaffold, expressing the typical ECM production for tendon in the aligned zone, or bone tissue in the random mineralized part. CS resulted in a synergistic effect, favoring cell adhesion/proliferation on the scaffold surface. These results suggest that this tubular scaffold loaded with CS could be a powerful tool to support enthesis repair upon surgery.

In recent decades, the demand for replacement of damaged or broken tissues has increased; this poses the attention on problems related to low donor availability. For this reason, researchers focused their attention on the field of tissue engineering, which allows the development of scaffolds able to mimic the tissues' extracellular matrix. However, tissue replacement and regeneration are complex since scaffolds need to guarantee an adequate hierarchical structured morphology as well as adequate mechanical, chemical, and physical properties to stand the stresses and enhance the new tissue formation. For this purpose, the use of inorganic materials as fillers for the scaffolds has gained great interest in tissue engineering applications, due to their wide range of physicochemical properties as well as their capability to induce biological responses. However, some issues still need to be faced to improve their efficacy. This review focuses on the description of the most effective inorganic nanomaterials (clays, nano-based nanomaterials, metal oxides, metallic nanoparticles) used in tissue engineering and their properties. Particular attention has been devoted to their combination with scaffolds in a wide range of applications. In particular, skin, orthopaedic, and neural tissue engineering have been considered.

The goal of this work is the design and the development of scaffolds based on maltodextrin (MD) to recover chronic lesions. MD was mixed with arginine/lysine/polylysine and the electrospinning was successfully used to prepare scaffolds with uniform and continuous nanofibers having regular shape and smooth surface. A thermal treatment was applied to obtain insoluble scaffolds in aqueous environment, taking the advantage of amino acids-polysaccharide conjugates formed via Maillard-type reaction. The morphological analysis showed that the scaffolds had nanofibrous structures, and that the cross-linking by heating did not significantly change the nanofibers' dimensions and did not alter the system stability. Moreover, the heating process caused a reduction of free amino group and proportionally increased scaffold cross-linking degree. The scaffolds were elastic and resistant to break, and possessed negative zeta potential in physiological fluids. These were characterized by direct antioxidant properties and Fe 2+ chelation capability (indirect antioxidant properties). Moreover, the scaffolds were cytocompatible towards fibroblasts and monocytes-derived macrophages, and did not show any significant pro-inflammatory activity. Finally, those proved to accelerate the recovery of the burn/excisional wounds. Considering all the features, MD-poly/amino acids scaffolds could be considered as promising medical devices for the treatment of chronic wounds., 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 © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The spontaneous healing of a tendon laceration results in the formation of scar tissue, which has lower functionality than the original tissue. Moreover, chronic non-healing tendon injuries frequently require surgical treatment. Several types of scaffolds have been developed using the tissue engineering approach, to complement surgical procedures and to enhance the healing process at the injured site. In this work, an electrospun hybrid tubular scaffold was designed to mimic tissue fibrous arrangement and extracellular matrix (ECM) composition, and to be extemporaneously loaded into the inner cavity with human platelet lysate (PL), with the aim of leading to complete post-surgery functional regeneration of the tissue for functional regeneration of the osteo-tendon interface. For this purpose, pullulan (P)/chitosan (CH) based polymer solutions were enriched with hydroxyapatite nanoparticles (HP) and electrospun. The nanofibers were collected vertically along the length of the scaffold to mimic the fascicle direction of the tendon tissue. The scaffold obtained showed tendon-like mechanical performance, depending on HP content and tube size. The PL proteins were able to cross the scaffold wall, and in vitro studies have demonstrated that tenocytes and osteoblasts are able to adhere to and proliferate onto the scaffold in the presence of PL; moreover, they were also able to produce either collagen or sialoproteins, respectively-important components of ECM. These results suggest that HP and PL have a synergic effect, endorsing PL-loaded HP-doped aligned tubular scaffolds as an effective strategy to support new tissue formation in tendon-to-bone interface regeneration.

Prcis: Ambulatory blood pressure (BP) and intraocular pressure (IOP) monitoring of patients with normal tension glaucoma (NTG) revealed features of vascular dysregulation including hypertension, blunted nocturnal BP dipping, and morning BP surge., Purpose: The aim was to examine ambulatory fluctuations in IOP and BP in patients with NTG., Methods: A prospective study of 45 participants with NTG and 10 controls. All participants had a comprehensive ophthalmological examination followed by glaucoma medication washout. Patients using systemic antihypertensives were excluded. IOP and BP were recorded using home monitoring over 48 hours using a self-rebound tonometer and ambulatory blood pressure monitor. BP was recorded every 30 minutes by day and every 60 minutes overnight. IOP was recorded at 09:00, 11:00, 13:00, 16:00, 20:00, and 04:00., Results: Participants with NTG had a median mean deviation (MD) of -4.66 dB (interquartile range: -7.16 to -2.81 dB) in the worse eye. Among those with glaucoma, 18 of 45 (40%) had normal nocturnal BP dipping, 24 (53%) blunted dipping and 3 (6.7%) exaggerated dipping. Each 10 mm Hg lower minimum sleeping systolic BP was associated with a 0.9 dB (95% confidence interval: 0.1-1.6 dB) worse MD. Sixteen of 45 participants with glaucoma (35.6%) and 1 of 10 controls (10%) were found to have systemic hypertension on ambulatory blood pressure monitoring and 32 of those with glaucoma (71%) had a surge in morning BP, compared with 5 controls (50%). There was no difference in MD between patients with normal, exaggerated and blunted dipping (P=0.813)., Conclusions: Though glaucoma has been associated with exaggerated nocturnal BP dipping, we found a higher proportion of patients had systemic hypertension, blunted nocturnal BP dipping, and a morning BP surge, measures also associated with vascular dysregulation., Competing Interests: Disclosure: A.J.T.: Research support (Allergan), Speaker (Allergan, Heidelberg Engineering, Santen, Thea); Consultant (Thea, Santen, Allergan). The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with ocular hypertension (OHT) and glaucoma are increasingly reviewed in virtual clinics. As the clinician is not present during the patient's visit it is important that measurements obtained are reliable. The aim of this study was to examine agreement between Goldmann Applanation Tonometry (GAT) intraocular pressure (IOP) measurements (obtained by ophthalmologists and ophthalmic nurses) and a newer automated tonometer-the Ocular Response Analyzer (ORA)., Methods: A prospective study was conducted including 116 eyes of 116 patients with glaucoma and OHT. All subjects had GAT IOP obtained by a nurse and ophthalmologist and ORA IOP by a technician. The order of testing was randomised and previous measurements were masked. Agreement was examined using Bland-Altman plots and 95% limits of agreement (LoA). Intraclass correlation coefficients (ICC) of repeat GAT and ORA measurements were calculated., Results: Patients had a mean age of 70 ± 13 years. The 95% LoA between ophthalmologist (mean: 14.6 ± 4.3 mmHg) and nurse (mean: 15.0 ± 4.0 mmHg) GAT measurements was ±5.21 mmHg, whereas the 95% LoA between repeat ORA IOPg (mean: 13.8 ± 4.7 mmHg) was ±2.52 mmHg. There was no proportional bias. The ICC was 0.972 for repeat IOPg compared with 0.863 for repeat GAT., Conclusions: There was only moderate agreement between GAT IOP measurements obtained by nurses working in the virtual clinic and ophthalmologists. Agreement between ORA IOP and ophthalmologists' GAT IOP was better and ORA produced more repeatable measurements, providing evidence it may be a more reliable tool for IOP assessment in virtual clinics.

The aim of this study was to investigate the relationship between glaucoma severity and perifoveal vessel density (pfVD), branching complexity, and foveal avascular zone (FAZ) size in normal tension glaucoma (NTG). 31 patients with NTG washed out of glaucoma medications were subjected to tests including; intraocular pressure measurement; standard automated perimetry; optical coherence tomography (OCT) measurement of macular ganglion cell complex (mGCC), inner macular thickness (IMT) and circumpapillary retinal nerve fibre layer (cpRNFL); and OCT angiography measurement of pfVD, FAZ perimeter and multispectral fractal dimensions (MSFD). Eyes with more severe glaucoma had significantly thinner mGCC and cpRNFL and lower pfVD. MD decreased by 0.4 dB (95% CI 0.1 to 0.6 dB, P = 0.007) for every 1% decrease in pfVD. Lower MSFD was observed in eyes with lower pfVD and in patients with systemic hypertension. Multivariable analysis, accounting for age and OCTA quality, found lower pfVD remained significantly associated with thinner IMT, thinner mGCC and worse MD but not with MSFD. pfVD was reduced in NTG and was diminished in eyes with worse MD. Macular vessel branching complexity was not related to severity of visual field loss but was lower in patients with systemic hypertension.

The tendon is a highly aligned connective tissue that transmits force from muscle to bone. Each year, more than 32 million tendon injuries have been reported, in fact, tendinopathies represent at least 50% of all sports injuries, and their incidence rates have increased in recent decades due to the aging population. Current clinical grafts used in tendon treatment are subject to several restrictions and there is a significant demand for alternative engineered tissue. For this reason, innovative strategies need to be explored. Tendon replacement and regeneration are complex since scaffolds need to guarantee an adequate hierarchical structured morphology and mechanical properties to stand the load. Moreover, to guide cell proliferation and growth, scaffolds should provide a fibrous network that mimics the collagen arrangement of the extracellular matrix in the tendons. This review focuses on tendon repair and regeneration. Particular attention has been devoted to the innovative approaches in tissue engineering. Advanced manufacturing techniques, such as electrospinning, soft lithography, and three-dimensional (3D) printing, have been described. Furthermore, biological augmentation has been considered, as an emerging strategy with great therapeutic potential.

Purpose: To generate the first open dataset of retinal parafoveal optical coherence tomography angiography (OCTA) images with associated ground truth manual segmentations, and to establish a standard for OCTA image segmentation by surveying a broad range of state-of-the-art vessel enhancement and binarization procedures., Methods: Handcrafted filters and neural network architectures were used to perform vessel enhancement. Thresholding methods and machine learning approaches were applied to obtain the final binarization. Evaluation was performed by using pixelwise metrics and newly proposed topological metrics. Finally, we compare the error in the computation of clinically relevant vascular network metrics (e.g., foveal avascular zone area and vessel density) across segmentation methods., Results: Our results show that, for the set of images considered, deep learning architectures (U-Net and CS-Net) achieve the best performance (Dice = 0.89). For applications where manually segmented data are not available to retrain these approaches, our findings suggest that optimally oriented flux (OOF) is the best handcrafted filter (Dice = 0.86). Moreover, our results show up to 25% differences in vessel density accuracy depending on the segmentation method used., Conclusions: In this study, we derive and validate the first open dataset of retinal parafoveal OCTA images with associated ground truth manual segmentations. Our findings should be taken into account when comparing the results of clinical studies and performing meta-analyses. Finally, we release our data and source code to support standardization efforts in OCTA image segmentation., Translational Relevance: This work establishes a standard for OCTA retinal image segmentation and introduces the importance of evaluating segmentation performance in terms of clinically relevant metrics., Competing Interests: Disclosure: Y. Giarratano, None; E. Bianchi, None; C. Gray, None; A. Morris, None; T. MacGillivray, None; B. Dhillon, None; M.O. Bernabeu, None, (Copyright 2020 The Authors.)

Chronic wounds, such as pressure ulcers, diabetic ulcers, venous ulcers and arterial insufficiency ulcers, are lesions that fail to proceed through the normal healing process within a period of 12 weeks. The treatment of skin chronic wounds still represents a great challenge. Wound medical devices (MDs) range from conventional and advanced dressings, up to skin grafts, but none of these are generally recognized as a gold standard. Based on recent developments, this paper reviews nanotechnology-based medical devices intended as skin substitutes. In particular, nanofibrous scaffolds are promising platforms for wound healing, especially due to their similarity to the extracellular matrix (ECM) and their capability to promote cell adhesion and proliferation, and to restore skin integrity, when grafted into the wound site. Nanotechnology-based scaffolds are emphasized here. The discussion will be focused on the definition of critical quality attributes (chemical and physical characterization, stability, particle size, surface properties, release of nanoparticles from MDs, sterility and apyrogenicity), the preclinical evaluation (biocompatibility testing, alternative in vitro tests for irritation and sensitization, wound healing test and animal wound models), the clinical evaluation and the CE (European Conformity) marking of nanotechnology-based MDs.

Objective: To explore the views of senior doctors on mental illness within the medical profession., Background: There has been increasing interest on the issue of doctors' mental health. However, there have been few qualitative studies on senior doctors' general attitude towards mental illness within the medical profession., Setting: Large North London teaching hospital., Participants: 13 hospital consultants and senior academic general practitioners., Methods: A qualitative study involving semi-structured interviews and reflective work. The outcome measures were the themes derived from the thematic framework approach to analysis., Results: Four main themes were identified. (1) 'Doctors' attitudes to mental illness'-doctors felt that there remained a significant stigma attached to suffering from a mental illness within the profession. (2) 'Barriers to seeking help'-doctors felt that there were numerous barriers to seeking help such as negative career implications, being perceived as weak, denial and fear of prejudice. (3) 'Support'-doctors felt that the use of support depended on certainty concerning confidentiality, which for occupational health was not thought to be guaranteed. Confiding in colleagues was rare except among close friends. Supervision for all doctors was raised. (4) 'General Medical Council (GMC) involvement'-doctors felt that uneasy referring colleagues to the GMC and the appraisal and revalidation process was thought not to be thorough enough in picking up doctors with a mental illness., Conclusions: Owing to the small size of this study, the conclusions are limited; however, if the findings are confirmed by larger studies, they suggest that greater efforts are needed to destigmatise mental illness in the profession and improve support for doctors. Additional research should be carried out into doctors' views on occupational health services in managing doctors with mental illness, the provision of supervision for all doctors and the effectiveness of the current appraisal and revalidation process at identifying doctors with a mental illness., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

There is a paucity of data on the treatment outcome in children with relapsed or poorly responsive nodular lymphocyte predominant Hodgkin lymphoma (nLPHL). This retrospective report evaluates the treatment outcome in a national cohort of children with relapsed or poorly responsive nLPHL. A total of 37 patients, 22 with relapsed and 15 with poorly responding disease, are the subjects of this report. Of the 22 patients with relapsed nLPHL, 11 had relapsed after primary excision biopsy, 10 after chemotherapy and 1 after chemotherapy and involved field radiotherapy. The majority had localized disease at relapse. The median time to relapse was 8 months after chemotherapy and 11 months after excision biopsy. Seven of the 15 patients with poorly responding nLPHL had variant histology. Three patients with initial poor response did not receive any further treatment and have had no disease progression. Transformation to diffuse large B cell lymphoma, in addition to evolution from typical to variant nLPHL occurred in one patient each. Thirty-four patients have been successfully re-treated with second chemotherapy or radiotherapy. Multiple relapses were uncommon but treatable. Relapse or poorly responsive nLPHL is fully salvageable with either additional chemotherapy and or radiotherapy., (© 2016 John Wiley & Sons Ltd.)