Exploring young people's attitudes to HIV prevention medication (PrEP) in England: a qualitative study.

INTRODUCTION: Young people aged 18-24 years old are a key demographic target for eliminating HIV transmission globally. Pre-exposure prophylaxis (PrEP), a prevention medication, reduces HIV transmission. Despite good uptake by gay and bisexual men who have sex with men, hesitancy to use PrEP has been observed in other groups, such as young people and people from ethnic minority backgrounds. The aim of this study was to explore young people's perceptions and attitudes to using PrEP. DESIGN: A qualitative transcendental phenomenological design was used. PARTICIPANTS AND SETTING: A convenience sample of 24 young people aged between 18 and 24 years was recruited from England. METHODS: Semistructured interviews and graphical elicitation were used to collect data including questions about current experiences of HIV care, awareness of using PrEP and decision-making about accessing PrEP. Thematic and visual analyses were used to identify findings. RESULTS: Young people had good levels of knowledge about HIV but poor understanding of using PrEP. In this information vacuum, negative stigma and stereotypes about HIV and homosexuality were transferred to using PrEP, which were reinforced by cultural norms portrayed on social media, television and film-such as an association between using PrEP and being a promiscuous, white, gay male. In addition, young people from ethnic minority communities appeared to have negative attitudes to PrEP use, compared with ethnic majority counterparts. This meant these young people in our study were unable to make decisions about when and how to use PrEP. CONCLUSION: Findings indicate an information vacuum for young people regarding PrEP. A strength of the study is that theoretical data saturation was reached. A limitation of the study is participants were largely from Northern England, which has low prevalence of HIV. Further work is required to explore the information needs of young people in relation to PrEP.

Plant-derived compounds as potential leads for new drug development targeting COVID-19.

COVID-19, which was first identified in 2019 in Wuhan, China, is a respiratory illness caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although some patients infected with COVID-19 can remain asymptomatic, most experience a range of symptoms that can be mild to severe. Common symptoms include fever, cough, shortness of breath, fatigue, loss of taste or smell and muscle aches. In severe cases, complications can arise including pneumonia, acute respiratory distress syndrome, organ failure and even death, particularly in older adults or individuals with underlying health conditions. Treatments for COVID-19 include remdesivir, which has been authorised for emergency use in some countries, and dexamethasone, a corticosteroid used to reduce inflammation in severe cases. Biological drugs including monoclonal antibodies, such as casirivimab and imdevimab, have also been authorised for emergency use in certain situations. While these treatments have improved the outcome for many patients, there is still an urgent need for new treatments. Medicinal plants have long served as a valuable source of new drug leads and may serve as a valuable resource in the development of COVID-19 treatments due to their broad-spectrum antiviral activity. To date, various medicinal plant extracts have been studied for their cellular and molecular interactions, with some demonstrating anti-SARS-CoV-2 activity in vitro. This review explores the evaluation and potential therapeutic applications of these plants against SARS-CoV-2. This review summarises the latest evidence on the activity of different plant extracts and their isolated bioactive compounds against SARS-CoV-2, with a focus on the application of plant-derived compounds in animal models and in human studies.

Quantifiable Changes in the Submental Area and Mandible Border After Dual-Modality Treatment With ATX-101 and VYC-20L for Overall Improvement in Jawline Contour.

BACKGROUND: A phase 4, prospective, open-label, multicenter study showed that treatment with deoxycholic acid injections (ATX-10) followed by a hyaluronic acid filler (VYC-20L) is safe and effective for reducing submental fullness and improving jawline definition. OBJECTIVE: To quantify changes in the jawline and submental area using 3-dimensional (3D) photogrammetry and conduct an immunohistochemical analysis of submental tissue.  Methods: Participants received 1 to 6 ATX-101 treatments (8 weeks apart) followed by VYC-20L (optional touch-up after 14 days). Changes from baseline in jawline and submental volumes, submental major and minor strain events, submental skin displacement, and submental angles were quantified using photogrammetry. Submental skin biopsies (N=13) were excised for histologic analysis. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: Fifty-three participants were treated. From baseline to the final study visit, the mean volume increased for the jawline and decreased for the submental area. There was a larger percentage change from baseline in the minor versus major strain event, indicating greater skin surface compression than expansion within the submental area. Mean change from baseline in submental skin position indicated superior and posterior movement from a lateral perspective, while the mean submental angle decreased between baseline and exit. Collagen I and III expression significantly increased from baseline (P<0.05). All participants reported at least 1 TEAE; the majority were mild or moderate in severity. CONCLUSIONS: Dual-modality treatment with ATX-101 and VYC-20L reduces submental fat and improves jawline definition with quantifiable changes in jawline volume, submental volume, strain, skin displacement, and angle, as well as collagen expression. J Drugs Dermatol. 2024;23(1):1325-1331.        doi:10.36849/JDD.7458.

Poly(2-Hydroxyethyl Methacrylate) Hydrogel-Based Microneedles for Metformin Release.

The release of metformin, a drug used in the treatment of cancer and diabetes, from poly(2-hydroxyethyl methacrylate), pHEMA, hydrogel-based microneedle patches is demonstrated in vitro. Tuning the composition of the pHEMA hydrogels enables preparation of robust microneedle patches with mechanical properties such that they would penetrate skin (insertion force of a single microneedle to be ≈40 N). Swelling experiments conducted at 20, 35, and 60 °C show temperature-dependent degrees of swelling and diffusion kinetics. Drug release from the pHEMA hydrogel-based microneedles is fitted to various models (e.g., zero order, first order, second order). Such pHEMA microneedles have potential application for transdermal delivery of metformin for the treatment of aging, cancer, diabetes, etc.

Climate-smart forestry through innovative wood products and commercial afforestation and reforestation on marginal land.

Afforestation and reforestation (AR) on marginal land are nature-based solutions to climate change. There is a gap in understanding the climate mitigation potential of protection and commercial AR with different combinations of forest plantation management and wood utilization pathways. Here, we fill the gap using a dynamic, multiscale life cycle assessment to estimate one-century greenhouse gas (GHG) mitigation delivered by (both traditional and innovative) commercial and protection AR with different planting density and thinning regimes on marginal land in the southeastern United States. We found that innovative commercial AR generally mitigates more GHGs across 100 y (3.73 to 4.15 Giga tonnes of CO2 equivalent (Gt CO2e)) through cross-laminated timber (CLT) and biochar than protection AR (3.35 to 3.69 Gt CO2e) and commercial AR with traditional lumber production (3.17 to 3.51 Gt CO2e), especially in moderately cooler and dryer regions in this study with higher forest carbon yield, soil clay content, and CLT substitution. In a shorter timeframe (≤50 y), protection AR is likely to deliver higher GHG mitigation. On average, for the same wood product, low-density plantations without thinning and high-density plantations with thinning mitigate more life cycle GHGs and result in higher carbon stock than that of low-density with thinning plantations. Commercial AR increases the carbon stock of standing plantations, wood products, and biochar, but the increases have uneven spatial distributions. Georgia (0.38 Gt C), Alabama (0.28 Gt C), and North Carolina (0.13 Gt C) have the largest carbon stock increases that can be prioritized for innovative commercial AR projects on marginal land.

Electrochemically Enhanced Delivery of Pemetrexed from Electroactive Hydrogels.

Electroactive hydrogels based on derivatives of polyethyleneglycol (PEG), chitosan and polypyrrole were prepared via a combination of photopolymerization and oxidative chemical polymerization, and optionally doped with anions (e.g., lignin, drugs, etc.). The products were analyzed with a variety of techniques, including: FT-IR, UV-Vis, 1H NMR (solution state), 13C NMR (solid state), XRD, TGA, SEM, swelling ratios and rheology. The conductive gels swell ca. 8 times less than the non-conductive gels due to the presence of the interpenetrating network (IPN) of polypyrrole and lignin. A rheological study showed that the non-conductive gels are soft (G' 0.35 kPa, G″ 0.02 kPa) with properties analogous to brain tissue, whereas the conductive gels are significantly stronger (G' 30 kPa, G″ 19 kPa) analogous to breast tissue due to the presence of the IPN of polypyrrole and lignin. The potential of these biomaterials to be used for biomedical applications was validated in vitro by cell culture studies (assessing adhesion and proliferation of fibroblasts) and drug delivery studies (electrochemically loading the FDA-approved chemotherapeutic pemetrexed and measuring passive and stimulated release); indeed, the application of electrical stimulus enhanced the release of PEM from gels by ca. 10-15% relative to the passive release control experiment for each application of electrical stimulation over a short period analogous to the duration of stimulation applied for electrochemotherapy. It is foreseeable that such materials could be integrated in electrochemotherapeutic medical devices, e.g., electrode arrays or plates currently used in the clinic.

Can We Deliver Person-Centred Obesity Care Across the Globe?

PURPOSE OF REVIEW: This article discusses what person-centred care is; why it is critically important in providing effective care of a chronic, complex disease like obesity; and what can be learnt from international best practice to inform global implementation. RECENT FINDINGS: There are four key principles to providing person-centred obesity care: providing care that is coordinated, personalised, enabling and delivered with dignity, compassion and respect. The Canadian 5AsT framework provides a co-developed person-centred obesity care approach that addresses complexity and is being tested internationally. Embedding person-centred obesity care across the globe will require a complex system approach to provide a framework for healthcare system redesign, advances in people-driven discovery and advocacy for policy change. Additional training, tools and resources are required to support local implementation, delivery and evaluation. Delivering high-quality, effective person-centred care across the globe will be critical in addressing the current obesity epidemic.

Instructive electroactive electrospun silk fibroin-based biomaterials for peripheral nerve tissue engineering.

Aligned sub-micron fibres are an outstanding surface for orienting and promoting neurite outgrowth; therefore, attractive features to include in peripheral nerve tissue scaffolds. A new generation of peripheral nerve tissue scaffolds is under development incorporating electroactive materials and electrical regimes as instructive cues in order to facilitate fully functional regeneration. Herein, electroactive fibres composed of silk fibroin (SF) and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) were developed as a novel peripheral nerve tissue scaffold. Mats of SF with sub-micron fibre diameters of 190 ± 50 nm were fabricated by double layer electrospinning with thicknesses of ∼100 µm (∼70-80 µm random fibres and ∼20-30 µm aligned fibres). Electrospun SF mats were modified with interpenetrating polymer networks (IPN) of PEDOT:PSS in various ratios of PSS/EDOT (α) and the polymerisation was assessed by hard X-ray photoelectron spectroscopy (HAXPES). The mechanical properties of electrospun SF and IPNs mats were characterised in the wet state tensile and the electrical properties were examined by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The cytotoxicity and biocompatibility of the optimal IPNs (α = 2.3 and 3.3) mats were ascertained via the growth and neurite extension of mouse neuroblastoma x rat glioma hybrid cells (NG108-15) for 7 days. The longest neurite outgrowth of 300 µm was observed in the parallel direction of fibre alignment on laminin-coated electrospun SF and IPN (α = 2.3) mats which is the material with the lowest electron transfer resistance (Ret, ca. 330 Ω). These electrically conductive composites with aligned sub-micron fibres exhibit promise for axon guidance and also have the potential to be combined with electrical stimulation treatment as a further step for the effective regeneration of nerves.

Controlled Bioactive Delivery Using Degradable Electroactive Polymers.

Biomaterials capable of precisely controlling the delivery of agrochemicals/biologics/drugs/fragrances have significant markets in the agriscience/healthcare industries. Here, we report the development of degradable electroactive polymers and their application for the controlled delivery of a clinically relevant drug (the anti-inflammatory dexamethasone phosphate, DMP). Electroactive copolymers composed of blocks of polycaprolactone (PCL) and naturally occurring electroactive pyrrole oligomers (e.g., bilirubin, biliverdin, and hemin) were prepared and solution-processed to produce films (optionally doped with DMP). A combination of in silico/in vitro/in vivo studies demonstrated the cytocompatibility of the polymers. The release of DMP in response to the application of an electrical stimulus was observed to be enhanced by ca. 10-30% relative to the passive release from nonstimulated samples in vitro. Such stimuli-responsive biomaterials have the potential for integration devices capable of delivering a variety of molecules for technical/medical applications.

Drug repurposing: Misconceptions, challenges, and opportunities for academic researchers.

Drug repurposing is promoted as a cost- and time-effective mechanism for providing new medicines. Often, however, there is insufficient consideration by academic researchers of the processes required to ensure that a repurposed drug can be used for a new indication. This may explain the inability of drug repurposing to fulfill its promise. Important aspects, often overlooked, include financial and intellectual property considerations, the clinical and regulatory path, and clinical equipoise, which provides ethical justification for randomized controlled trials. The goal of drug repurposing is to obtain a new regulator-approved label for an existing drug, and so, the trajectory for drug repurposing and traditional drug development is similar. Here, we discuss factors critical for a successful repurposed medicine to help academic investigators better identify drug repurposing opportunities.

Tips on Raising Reliable Local Perforator Flaps.

From early on in the development of plastic surgery, it was quickly realized that utilizing locally adjacent tissue, or "matching like with like," yielded superior aesthetic reconstructions to those in which the tissue was derived from a distant location. In many cases, the use of a local perforator flap is a simpler procedure with less patient morbidity and a quicker recovery from surgery. The difficulty with local perforator flaps has been locating the supplying perforators, ensuring that the flap has a robust and reliable blood supply, and that sufficient tissue is able to be transferred. The recent reappraisal of our understanding of the blood supply of the integument has allowed, for the first time, the capacity to accurately and inexpensively, without the need for "high tech equipment," locate perforators, as they emerge from the deep fascia into the overlying integument, and through a better understanding of the interconnecting anastomotic vessels between perforators reliably predict how much tissue can be safely raised on a single perforator, before surgery. Further, through the use of strategic "delay," it is possible to manipulate the interconnecting vessels between the selected perforator and its surrounding neighbors to design a flap of tissue of any dimension, composed of whatever tissue we require, and safely transfer that tissue locally, or if required, distantly, as a free flap. This article will highlight these advances, explain their relevance in raising reliable local perforator flaps, and will, where possible, call attention to any pearls and pitfalls, and how to avoid complications.

Electrically Conductive and 3D-Printable Oxidized Alginate-Gelatin Polypyrrole:PSS Hydrogels for Tissue Engineering.

Electroactive hydrogels can be used to influence cell response and maturation by electrical stimulation. However, hydrogel formulations which are 3D printable, electroactive, cytocompatible, and allow cell adhesion, remain a challenge in the design of such stimuli-responsive biomaterials for tissue engineering. Here, a combination of pyrrole with a high gelatin-content oxidized alginate-gelatin (ADA-GEL) hydrogel is reported, offering 3D-printability of hydrogel precursors to prepare cytocompatible and electrically conductive hydrogel scaffolds. By oxidation of pyrrole, electroactive polypyrrole:polystyrenesulfonate (PPy:PSS) is synthesized inside the ADA-GEL matrix. The hydrogels are assessed regarding their electrical/mechanical properties, 3D-printability, and cytocompatibility. It is possible to prepare open-porous scaffolds via bioplotting which are electrically conductive and have a higher cell seeding efficiency in scaffold depth in comparison to flat 2D hydrogels, which is confirmed via multiphoton fluorescence microscopy. The formation of an interpenetrating polypyrrole matrix in the hydrogel matrix increases the conductivity and stiffness of the hydrogels, maintaining the capacity of the gels to promote cell adhesion and proliferation. The results demonstrate that a 3D-printable ADA-GEL can be rendered conductive (ADA-GEL-PPy:PSS), and that such hydrogel formulations have promise for cell therapies, in vitro cell culture, and electrical-stimulation assisted tissue engineering.

Increasing Perfusion Pressure Does Not Distend Perforators or Anastomoses but Reveals Arteriovenous Shuntings.

BACKGROUND: It has been proposed that hyperperfusion of perforators and distension of anastomotic vessels may be a mechanism by which large perforator flaps are perfused. This study investigates whether increasing perfusion pressure of radiographic contrast in cadaveric studies altered the radiographic appearance of vessels, particularly by distending their anastomotic connections. METHODS: From 10 fresh cadavers, bilateral upper limbs above the elbow were removed. Three cadavers were excluded. Seven pairs of limbs were injected with lead oxide solutions via the brachial artery while distally monitoring intravascular pressure in the radial artery using a pressure transducer. One limb was injected slowly (0.5 mL/s) and the other rapidly (1.5 mL/s) to produce low and high perfusion pressures, respectively. Skin and subcutaneous tissue were then removed and radiographed. RESULTS: The filling of perforators and their larger caliber branches appeared unchanged between low- and high-pressure injections, with no significant increase in true anastomoses (P = 0.32) and no association between maximum perfusion pressure and number (P = 0.94) or caliber (P = 0.10). However, high-pressure injections revealed arteriovenous shunting with filling of the tributaries of the major veins. CONCLUSIONS: This study demonstrated that increased perfusion pressure of the cutaneous arteries (1) did not change the caliber of vessels; (2) did not convert choke to true anastomoses; and (3) revealed arteriovenous shunting between major vessels with retrograde filling of venous tributaries as pressure increased. This suggests that it is not possible to distend anastomotic connections between vascular territories by increasing perfusion alone.

Electroresponsive Silk-Based Biohybrid Composites for Electrochemically Controlled Growth Factor Delivery.

Stimuli-responsive materials are very attractive candidates for on-demand drug delivery applications. Precise control over therapeutic agents in a local area is particularly enticing to regulate the biological repair process and promote tissue regeneration. Macromolecular therapeutics are difficult to embed for delivery, and achieving controlled release over long-term periods, which is required for tissue repair and regeneration, is challenging. Biohybrid composites incorporating natural biopolymers and electroconductive/active moieties are emerging as functional materials to be used as coatings, implants or scaffolds in regenerative medicine. Here, we report the development of electroresponsive biohybrid composites based on Bombyx mori silkworm fibroin and reduced graphene oxide that are electrostatically loaded with a high-molecular-weight therapeutic (i.e., 26 kDa nerve growth factor-ß (NGF-ß)). NGF-ß-loaded composite films were shown to control the release of the drug over a 10-day period in a pulsatile fashion upon the on/off application of an electrical stimulus. The results shown here pave the way for personalized and biologically responsive scaffolds, coatings and implantable devices to be used in neural tissue engineering applications, and could be translated to other electrically sensitive tissues as well.

The Functional Anatomy of the Ophthalmic Angiosome and Its Implications in Blindness as a Complication of Cosmetic Facial Filler Procedures.

BACKGROUND: Blindness following facial filler procedures, although rare, is devastating, usually acute, permanent, and attributed to an ophthalmic artery embolus. However, blindness may be delayed for up to 2 weeks, sometimes following injection at remote sites, suggesting alternative pathways and pathogenesis. METHODS: Seeking solutions, fresh cadaver radiographic lead oxide injection, dissection, and histologic studies of the orbital and facial pathways of the ophthalmic angiosome, performed by the ophthalmic artery and vein, both isolated and together, and facial artery perfusions, were combined with total body archival arterial and venous investigations. RESULTS: These revealed (1) arteriovenous connections between the ophthalmic artery and vein in the orbit and between vessels in the inner canthus, allowing passage of large globules of lead oxide; (2) the glabella, inner canthi, and nasal dorsum are the most vulnerable injection sites because ophthalmic artery branches are anchored to the orbital rim as they exit, a plexus of large-caliber avalvular veins drain into the orbits, and arteriovenous connections are present; (3) choke anastomoses between posterior and anterior ciliary vessels supplying the choroid and eye muscles may react with spasm to confine territories impacted with ophthalmic artery embolus; (4) true anastomoses exist between ophthalmic and ipsilateral or contralateral facial arteries, without reduction in caliber, permitting unobstructed embolus from remote sites; and (5) ophthalmic and facial veins are avalvular, allowing reverse flow. CONCLUSION: The authors' study has shown potential arterial and venous pathways for filler embolus to cause blindness or visual field defects, and is supported clinically by a review of the case literature of blindness following facial filler injection.

The development of a predictive model to identify potential HIV-1 attachment inhibitors.

Despite the significant progress in managing patients infected with HIV through the development of Highly Active Anti-Retroviral Therapy (HAART), major challenges and opportunities remain to be explored. Of particular interest, is the binding of glycoprotein 120 (gp120) to the primary cellular receptor Cluster of Differentiation 4 (CD4). In this work we describe our two phased computational process to identify useful compounds capable of binding to the gp120 protein for therapeutic purposes. We identified 187 compounds from the literature that conform to active binding sites on these proteins and use these as training/test sets. The data in the form of quantitative structure-activity relationships (QSAR) is downloaded from the ZINC database and transformed using principal components analysis. In the first phase we developed a Radial Basis Function neural network model that identifies potential inhibitors from a virtual screen of a subset of the ZINC database. In the second phase we modelled the top performing compounds using the Discovery Studio docking and screening software. By employing this approach, we identified that those compounds with a LogP value of approx 2-4 performed well in the binding simulations while the lower scoring compounds do not bind well.

A new selective pharmacological enhancer of the Orai1 Ca2+ channel reveals roles for Orai1 in smooth and skeletal muscle functions.

Store operated calcium (Ca2+) entry is an important homeostatic mechanism in cells, whereby the release of Ca2+ from intracellular endoplasmic reticulum stores triggers the activation of a Ca2+ influx pathway. Mediated by Orai1, this Ca2+ influx has specific and essential roles in biological processes as diverse as lactation to immunity. Although pharmacological inhibitors of this Ca2+ influx mechanism have helped to define the role of store operated Ca2+ entry in many cellular events, the lack of isoform specific modulators and activators of Orai1 has limited our full understanding of these processes. Here we report the identification and synthesis of an Orai1 activity enhancer that concurrently potentiated Orai1 Ca2+ -dependent inactivation (CDI). This unique enhancer of Orai1 had only a modest effect on Orai3 with weak inhibitory effects at high concentrations in intact MCF-7 breast cancer cells. The Orai1 enhancer heightened vascular smooth muscle cell migration induced by platelet-derived growth factor and the unique store operated Ca2+ entry pathway present in skeletal muscle cells. These studies show that IA65 is an exemplar for the translation and development of Orai isoform selective agents. The ability of IA65 to activate CDI demonstrates that agents can be developed that can enhance Orai1-mediated Ca2+ influx but avoid the cytotoxicity associated with sustained Orai1 activation. IA65 and/or future analogues with similar Orai1 and CDI activating properties could be fine tuners of physiological processes important in specific disease states, such as cellular migration and immune cell function.

Legacy forest structure increases bird diversity and abundance in aging young forests.

Many studies have demonstrated the importance of early-successional forest habitat for breeding bird abundance, composition, and diversity. However, very few studies directly link measures of bird diversity, composition and abundance to measures of forest composition, and structure and their dynamic change over early succession. This study examines the relationships between breeding bird community composition and forest structure in regenerating broadleaf forests of southern New England, USA, separating the influences of ecological succession from retained stand structure. We conducted bird point counts and vegetation surveys across a chronosequence of forest stands that originated between 2 and 24 years previously in shelterwood timber harvests, a silvicultural method of regenerating oak-mixed broadleaf forests. We distinguish between vegetation variables that relate to condition of forest regeneration and those that reflect legacy stand structure. Using principal components analyses, we confirmed the distinction between regeneration and legacy vegetation variables. We ran regression analysis to test for relationships between bird community variables, including nesting and foraging functional guild abundances, and vegetation variables. We confirmed these relationships with hierarchical partitioning. Our results demonstrate that regenerating and legacy vegetation correlate with bird community variables across stand phases and that the strength with which they drive bird community composition changes with forest succession. While measures of regeneration condition explain bird abundance and diversity variables during late initiation, legacy stand structure explains them during stem exclusion. Canopy cover, ground-story diversity, and canopy structure diversity are the most powerful and consistent explanatory variables. Our results suggest that leaving varied legacy stand structure to promote habitat heterogeneity in shelterwood harvests contributes to greater bird community diversity. Interestingly, this is particularly important during the structurally depauperate phase of stem exclusion of young regenerating forests.

Fragmentation reduces community-wide taxonomic and functional diversity of dispersed tree seeds in the Central Amazon.

The Amazon harbors one of the most diverse tree floras on earth, and most species depend on mutualists for pollination and seed dispersal. This makes them susceptible to reproductive decline in fragmented forest because many of these mutualists suffer area-related extinction in fragments. It remains unknown, however, whether this highly biodiverse tree flora will reproduce and ultimately persist in fragmented forest. We conducted a 2-yr study of seed fall in an experimentally fragmented, highly diverse Central Amazonian forest. We determined the effect of fragment size (1, 10, 100 ha and continuous forest control) on the density, species richness, functional diversity and functional composition of seeds separated into two data sets: dispersed tree seeds, and undispersed tree seeds. Our results show a 3× reduction in the density of undispersed, non-pioneer tree seeds in fragments of all sizes, indicating reduced seed production of the non-pioneer tree community. The density of dispersed tree seeds was reduced by 6× in fragments of all sizes, while species richness was reduced by 6× in 1-ha fragments and by 3× in 10- and 100-ha fragments compared to intact forest. This provides evidence of reduced community-wide seed dispersal, which became more pronounced with declining fragment size. The functional diversity (FRic) of dispersed tree seeds was reduced 9.6× in small fragments, and significant shifts in the functional composition for 8 of the 10 reproductive and ecological traits studied were identified, suggesting compromised ecosystem functioning. These functional compositional shifts provide evidence for disrupted mutualistic processes in fragments, which include loss of pollination by bees, especially small eusocial (meliponid) bees, and loss of dispersal by primates and large birds, which reduced the frequency of large-seeded tree species. Fragments also lost rare and mature-forest species, and collectively these changes suggest that future tree communities in fragmented Amazonian landscapes will retain a taxonomically and functionally impoverished species pool with a biased functional composition unless efforts are undertaken to conserve dispersal by large frugivores and pollination by meliponid bees.

The quadriceps Femoris allograft as an extension of the Angiosome concept: A cadaveric-based anatomical feasibility study.

BACKGROUND: Vascularised composite allo-transplantation (VCA) is emerging as a tailored approach for complex tissue reconstruction. This study focuses on the quadriceps VCA as a potential solution for tissue repair, following trauma, necrotising fasciitis/myositis, or tumor ablation. METHODS: Dissections were undertaken in 10 adult cadaveric lower limbs to characterize the blood supply to the quadriceps femoris for en bloc muscle allo-transplantation. A mock cadaveric transplantation was performed to (a) define the best neurovascular VCA design and (b) test the feasibility of the procedure. A review of 54 archival radiograph studies from the institution was also performed to further evaluate the muscle vasculature. RESULTS: In two lower limbs, the quadriceps VCA was harvested designed on the common and superficial femoral vessels and nerve, which revealed a lengthy and bloody dissection, especially of the veins, which could increase clinically with the inability to use a tourniquet for most of the dissection. However, review of our previous archival studies showed that all four quadriceps muscles are supplied within the lateral circumflex femoral angiosome. In a further eight lower limbs, the quadriceps femoris muscle group consistently received its blood supply from the lateral circumflex femoral angiosome, verified by selective lead oxide injections of this artery. The vastus medialis appeared to have a more tenous blood supply distally based on this angiosome. A successful mock cadaveric transplant was performed based on this data. CONCLUSIONS: We suggest that the best neuromuscular quadriceps VCA should be (a) designed on the lateral circumflex femoral pedicle, (b) should be raised from distal to proximal, and (c) should include the descending genicular vessels as a potential supplemental supply to vastus medialis, should all four muscles be required.