Nonsurgical Management of Adductor-related groin pain with Ultrasound-Guided Platelet-Rich Plasma Injection and Physical Therapy in a Competitive Soccer Player: A Case Report.

Introduction: Adductor-related groin pain involves an injury to the common aponeurosis connecting the rectus abdominus and adductor longus to the pubis. It commonly occurs in sports that require cutting and pivoting and can result in significant loss of playing time. Platelet-Rich Plasma (PRP) is often indicated for treatment of musculoskeletal disorders and may represent an alternative treatment for patients with adductor-related groin pain. The purpose of this case report is to describe the non-surgical management of adductor-related groin pain in a competitive soccer player with a with an ultrasound (US)-guided PRP injection and physical therapy management. Case Description: A 17-year-old male competitive soccer player with right-sided adductor-related groin pain was treated with an US-guided PRP and a multi-phased physical therapy regimen based on tissue healing and individual patient/criteria progression. The patient completed 12 physical therapy sessions over six weeks post PRP injection. Outcomes: At the end of treatment, clinically meaningful improvements were observed in pain intensity, passive range of motion, strength (handheld dynamometry, Biodex), functional tests, psychosocial (OSPRO-YF) and patient-reported outcomes (HAGOS, LEFS). The subject returned to sport at six weeks post injection without limitation and at three months follow up, the subject reported that he had returned to 95% of his previous level of play. Discussion: This case report may offer support for PRP as an alternative treatment in the management of adductor-related groin pain. Incorporation of PRP as an adjunct to physical therapy led to improvements on all outcomes that surpassed the clinical significance change criteria. Level of evidence: 5.

The 2022 top 10 list of endoscopy topics in medical publishing: an annual review by the American Society for Gastrointestinal Endoscopy Editorial Board.

Using a systematic literature search of original articles published during 2022 in Gastrointestinal Endoscopy and other high-impact medical and gastroenterology journals, the 10-member Editorial Board of the American Society for Gastrointestinal Endoscopy composed a list of the 10 most significant topic areas in GI endoscopy during the study year. Each Editorial Board member was directed to consider 3 criteria in generating candidate lists-significance, novelty, and global impact on clinical practice-and subject matter consensus was facilitated by the Chair through electronic voting. The 10 identified areas collectively represent advances in the following endoscopic spheres: artificial intelligence, endoscopic submucosal dissection, Barrett's esophagus, interventional EUS, endoscopic resection techniques, pancreaticobiliary endoscopy, management of acute pancreatitis, endoscopic environmental sustainability, the NordICC trial, and spiral enteroscopy. Each board member was assigned a consensus topic area around which to summarize relevant important articles, thereby generating this précis of the "top 10" endoscopic advances of 2022.

Cascading effects of climate change on recreational marine flats fishes and fisheries.

Tropical and subtropical coastal flats are shallow regions of the marine environment at the intersection of land and sea. These regions provide myriad ecological goods and services, including recreational fisheries focused on flats-inhabiting fishes such as bonefish, tarpon, and permit. The cascading effects of climate change have the potential to negatively impact coastal flats around the globe and to reduce their ecological and economic value. In this paper, we consider how the combined effects of climate change, including extremes in temperature and precipitation regimes, sea level rise, and changes in nutrient dynamics, are causing rapid and potentially permanent changes to the structure and function of tropical and subtropical flats ecosystems. We then apply the available science on recreationally targeted fishes to reveal how these changes can cascade through layers of biological organization-from individuals, to populations, to communities-and ultimately impact the coastal systems that depend on them. We identify critical gaps in knowledge related to the extent and severity of these effects, and how such gaps influence the effectiveness of conservation, management, policy, and grassroots stewardship efforts.

The impacts of mangrove range expansion on wetland ecosystem services in the southeastern United States: Current understanding, knowledge gaps, and emerging research needs.

Climate change is transforming ecosystems and affecting ecosystem goods and services. Along the Gulf of Mexico and Atlantic coasts of the southeastern United States, the frequency and intensity of extreme freeze events greatly influence whether coastal wetlands are dominated by freeze-sensitive woody plants (mangrove forests) or freeze-tolerant grass-like plants (salt marshes). In response to warming winters, mangroves have been expanding and displacing salt marshes at varying degrees of severity in parts of north Florida, Louisiana, and Texas. As winter warming accelerates, mangrove range expansion is expected to increasingly modify wetland ecosystem structure and function. Because there are differences in the ecological and societal benefits that salt marshes and mangroves provide, coastal environmental managers are challenged to anticipate the effects of mangrove expansion on critical wetland ecosystem services, including those related to carbon sequestration, wildlife habitat, storm protection, erosion reduction, water purification, fisheries support, and recreation. Mangrove range expansion may also affect wetland stability in the face of extreme climatic events and rising sea levels. Here, we review the current understanding of the effects of mangrove range expansion and displacement of salt marshes on wetland ecosystem services in the southeastern United States. We also identify critical knowledge gaps and emerging research needs regarding the ecological and societal implications of salt marsh displacement by expanding mangrove forests. One consistent theme throughout our review is that there are ecological trade-offs for consideration by coastal managers. Mangrove expansion and marsh displacement can produce beneficial changes in some ecosystem services, while simultaneously producing detrimental changes in other services. Thus, there can be local-scale differences in perceptions of the impacts of mangrove expansion into salt marshes. For very specific local reasons, some individuals may see mangrove expansion as a positive change to be embraced, while others may see mangrove expansion as a negative change to be constrained.

Urban-Rural Differences in the Epidemiology of Asthma and Allergies in Nigeria: A Population-Based Study.

PURPOSE: Urbanization is associated with the risk of developing allergic conditions. Few studies have evaluated the urban-rural disparity of allergic diseases in sub-Saharan Africa. OBJECTIVE: To compare the epidemiology of adult asthma and allergies in urban and rural Nigeria. SUBJECTS AND METHODS: A population-based cross-sectional study was performed among 910 subjects in Kwara State, North Central Nigeria, comprising 635 urban and 275 rural adults who were randomly selected. We used standardized questionnaires for data collection. RESULTS: The age-adjusted prevalence of adults reporting a previous "asthma attack" or "currently taking asthma medication" within the preceding 12 months (ECRHS asthma definition) was 3.4% urban, 0.5% rural, current allergic rhinoconjunctivitis (26.2% urban, 22.2% rural), and current skin allergy (13.9% urban, 10.5% rural). The age-adjusted prevalence of "physician-diagnosed allergic conditions": asthma (3.3% urban, 1.5% rural), allergic rhinoconjunctivitis (4.9% urban, 3.2% rural), and skin allergy (4.8% urban, 4.6% rural) were higher in urban areas than in rural areas. Urban areas recorded a higher age-adjusted 12 months prevalence of wheezing, night waking by breathlessness, night waking by chest tightness, asthma attack (p=0.042), and current use of asthma medication (p=0.031) than the rural areas. In the urban areas, 81% of those with asthma significantly had current allergic rhinoconjunctivitis, and 40.5% had current skin allergy, whereas in the rural areas, all subjects with asthma had current allergic rhinoconjunctivitis and 12.5% had current skin allergy (p=0.482). The most common trigger for asthma attack/respiratory symptoms among the urban household was exposure to environmental smoke (17.2%), and among the rural household, it was dust exposure (18.2%). Living in urban areas significantly increased the odds of having asthma [aOR: 5.6 (95% CI:1.6-19.6)] and allergic rhinoconjunctivitis [aOR: 1.7 (95% CI: 1.2-2.4)]. CONCLUSION: This study shows that urban residents frequently reported more allergic and respiratory symptoms and were at risk of having asthma and allergic rhinitis compared to rural residents. The findings would assist the physicians in understanding the urban-rural differences in the occurrence of allergic conditions, symptom triggers, and comorbidity, which are relevant in patient's clinical evaluation, treatment, and disease prevention.

Short Duration Alagebrium Chloride Therapy Prediabetes Does Not Inhibit Progression to Autoimmune Diabetes in an Experimental Model.

Mechanisms by which advanced glycation end products (AGEs) contribute to type 1 diabetes (T1D) pathogenesis are poorly understood. Since life-long pharmacotherapy with alagebrium chloride (ALT) slows progression to experimental T1D, we hypothesized that acute ALT therapy delivered prediabetes, may be effective. However, in female, non-obese diabetic (NODShiLt) mice, ALT administered prediabetes (day 50-100) did not protect against experimental T1D. ALT did not decrease circulating AGEs or their precursors. Despite this, pancreatic ß-cell function was improved, and insulitis and pancreatic CD45.1+ cell infiltration was reduced. Lymphoid tissues were unaffected. ALT pre-treatment, prior to transfer of primed GC98 CD8+ T cell receptor transgenic T cells, reduced blood glucose concentrations and delayed diabetes, suggesting islet effects rather than immune modulation by ALT. Indeed, ALT did not reduce interferon-γ production by leukocytes from ovalbumin-pre-immunised NODShiLt mice and NODscid recipients given diabetogenic ALT treated NOD splenocytes were not protected against T1D. To elucidate ß-cell effects, NOD-derived MIN6N8 ß-cell major histocompatibility complex (MHC) Class Ia surface antigens were examined using immunopeptidomics. Overall, no major changes in the immunopeptidome were observed during the various treatments with all peptides exhibiting allele specific consensus binding motifs. As expected, longer MHC Class Ia peptides were captured bound to H-2Db than H-2Kb under all conditions. Moreover, more 10-12 mer peptides were isolated from H-2Db after AGE modified bovine serum albumin (AGE-BSA) treatment, compared with bovine serum albumin (BSA) or AGE-BSA+ALT treatment. Proteomics of MIN6N8 cells showed enrichment of processes associated with catabolism, the immune system, cell cycling and presynaptic endocytosis with AGE-BSA compared with BSA treatments. These data show that short-term ALT intervention, given prediabetes, does not arrest experimental T1D but transiently impacts ß-cell function.

Implementation of the NHI (Normalized Hot Spot Indices) Algorithm on Infrared ASTER Data: Results and Future Perspectives.

The Normalized Hotspot Indices (NHI) tool is a Google Earth Engine (GEE)-App developed to investigate and map worldwide volcanic thermal anomalies in daylight conditions, using shortwave infrared (SWIR) and near infrared (NIR) data from the Multispectral Instrument (MSI) and the Operational Land Imager (OLI), respectively, onboard the Sentinel 2 and Landsat 8 satellites. The NHI tool offers the possibility of ingesting data from other sensors. In this direction, we tested the NHI algorithm for the first time on Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data. In this study, we show the results of this preliminary implementation, achieved investigating the Kilauea (Hawaii, USA), Klyuchevskoy (Kamchatka; Russia), Shishaldin (Alaska; USA), and Telica (Nicaragua) thermal activities of March 2000-2008. We assessed the NHI detections through comparison with the ASTER Volcano Archive (AVA), the manual inspection of satellite imagery, and the information from volcanological reports. Results show that NHI integrated the AVA observations, with a percentage of unique thermal anomaly detections ranging between 8.8% (at Kilauea) and 100% (at Shishaldin). These results demonstrate the successful NHI exportability to ASTER data acquired before the failure of SWIR subsystem. The full ingestion of the ASTER data collection, available in GEE, within the NHI tool allows us to develop a suite of multi-platform satellite observations, including thermal anomaly products from Landsat Thematic Mapper (TM) and Enhanced Thematic Mapper Plus (ETM+), which could support the investigation of active volcanoes from space, complementing information from other systems.

Testing the efficacy of lionfish traps in the northern Gulf of Mexico.

Spearfishing is currently the primary approach for removing invasive lionfish (Pterois volitans/miles) to mitigate their impacts on western Atlantic marine ecosystems, but a substantial portion of lionfish spawning biomass is beyond the depth limits of SCUBA divers. Innovative technologies may offer a means to target deepwater populations and allow for the development of a lionfish trap fishery, but the removal efficiency and potential environmental impacts of lionfish traps have not been evaluated. We tested a collapsible, non-containment trap (the 'Gittings trap') near artificial reefs in the northern Gulf of Mexico. A total of 327 lionfish and 28 native fish (four were species protected with regulations) recruited (i.e., were observed within the trap footprint at the time of retrieval) to traps during 82 trap sets, catching 144 lionfish and 29 native fish (one more than recruited, indicating detection error). Lionfish recruitment was highest for single (versus paired) traps deployed <15 m from reefs with a 1-day soak time, for which mean lionfish and native fish recruitment per trap were approximately 5 and 0.1, respectively. Lionfish from traps were an average of 19 mm or 62 grams larger than those caught spearfishing. Community impacts from Gittings traps appeared minimal given that recruitment rates were >10X higher for lionfish than native fishes and that traps did not move on the bottom during two major storm events, although further testing will be necessary to test trap movement with surface floats. Additional research should also focus on design and operational modifications to improve Gittings trap deployment success (68% successfully opened on the seabed) and reduce lionfish escapement (56% escaped from traps upon retrieval). While removal efficiency for lionfish demonstrated by traps (12-24%) was far below that of spearfishing, Gittings traps appear suitable for future development and testing on deepwater natural reefs, which constitute >90% of the region's reef habitat.

Poleward expansion of common snook Centropomus undecimalis in the northeastern Gulf of Mexico and future research needs.

Globally, rising temperatures have resulted in numerous examples of poleward shifts in species distribution patterns with accompanying changes in community structure and ecosystem processes. In the Gulf of Mexico, higher mean temperatures and less frequent winter freezes have led to the expansion of tropics-associated marine organisms. Our objectives were to quantify changing environmental conditions and the poleward expansion of the common snook Centropomus undecimalis into the Cedar Keys area of Florida, USA (29 deg N). The snook is an economically and recreationally important sport fish found from southern Brazil to south Florida. Cedar Key and the Lower Suwannee River are north of the snook's historically documented range, likely due to lethal water temperatures during winter. Using data from a long-term monitoring program, we report an increase in catches of snook in this area since 2007. The spatial and temporal expansion of the species began with adult fish in 2007. By 2018, snook of all sizes were found in the region, and we found strong evidence of local reproduction during 2016-2018. The locations of nursery habitat and winter thermal refuges (e.g., freshwater springs) need to be identified and have implications for land-use policy and minimum-flow regulations for rivers. The arrival of the snook in the northern Gulf of Mexico could affect food web ecology and habitat interactions among estuarine predators, and future studies should evaluate snook's food habits and competitive interactions with resident fishes in this expanded range. Our study provides an example of how species range expansions due to changing temperatures should result in new research priorities to evaluate impacts of climate change on coastal systems.

Precipitous Declines in Northern Gulf of Mexico Invasive Lionfish Populations Following the Emergence of an Ulcerative Skin Disease.

Invasive Indo-Pacific lionfish Pterois volitans/miles have become well-established in many western Atlantic marine habitats and regions. However, high densities and low genetic diversity could make their populations susceptible to disease. We examined changes in northern Gulf of Mexico (nGOM) lionfish populations following the emergence of an ulcerative skin disease in August 2017, when estimated disease prevalence was as high as 40%. Ulcerated female lionfish had 9% lower relative condition compared to non-ulcerated females. Changes in lionfish size composition indicated a potential recruitment failure in early summer 2018, when the proportion of new recruits declined by >80%. Remotely operated vehicle surveys during 2016-2018 indicated lionfish population density declined in 2018 by 75% on natural reefs. The strongest declines (77-79%) in lionfish density were on high-density (>25 lionfish per 100 m2) artificial reefs, which declined to similar levels as low-density (<15 lionfish per 100 m2) artificial reefs that had prior lionfish removals. Fisheries-dependent sampling indicated lionfish commercial spearfishing landings, commercial catch per unit effort (CPUE), and lionfish tournament CPUE also declined approximately 50% in 2018. Collectively, these results provide correlative evidence for density-dependent epizootic population control, have implications for managing lionfish and impacted native species, and improve our understanding of biological invasions.

Prevalence of asthma and respiratory symptoms during pregnancy in the middle belt of Nigeria.

Background: Information about the burden of asthma during pregnancy in Africa is scarce.Objectives: To determine the prevalence of asthma and respiratory symptoms in pregnancy in Ilorin, Nigeria.Methods: This study uses the European Community Respiratory Health Survey (ECRHS) questionnaire and definitions to screen 870 pregnant women attending three hospitals for asthma.Results: The prevalence of possible asthma (i.e. awakened by shortness of breath, asthma attack(s) in the last 12 months, or currently taking asthma medication) was 2.1% (95% CI: 1.3-3.1%), physician-diagnosed asthma was 1.0% (95% CI: 0.5-1.7%), and current asthma (asthma attack in the last 12 months and currently taking asthma medication) was 0.7% (95% CI: 0.2-1.3%). The prevalence of respiratory symptoms ranged from 0.6% (95% CI: 0.1-1.1%) for wheezing without cold to 12.9% (95% CI: 10.7-15.2%) for nasal allergies. Less than 1% reported an asthma attack and using asthma medication in the last 12 months. None of the pregnant women smoked tobacco during pregnancy. Pregnant women with possible asthma experienced more respiratory symptoms and worsening symptoms than those without asthma (15.8% vs. 3.9%), and the most reported symptom was being awakened by shortness of breath. The majority (55.6%) with physician-diagnosed asthma had suffered an asthma attack in the current pregnancy with a median of two attacks.Conclusion: The prevalence of asthma and respiratory symptoms in pregnancy in this sample was low, but we observed an increase and worsening of respiratory symptoms during pregnancy in those with asthma. Hence, the priority of clinicians should be disease control to prevent feto-maternal morbidity and mortality.

Systematic Incorporation of Sex-Specific Information Into Clinical Practice Guidelines for the Management of ST -Segment-Elevation Myocardial Infarction: Feasibility and Outcomes.

Background Clinical practice guideline ( CPG ) developers have yet to endorse a consistent and systematic approach for considering sex-specific cardiovascular information in CPG s. This article describes an initiative led by the Canadian Cardiovascular Society to determine the feasibility and outcomes of a structured process for considering sex in a CPG for the management of ST-segment-elevation myocardial infarction. Methods and Results A sex and gender champion was appointed to the guideline development committee. The feasibility of tailoring the CPG to sex was ascertained by recording (1) the male-female distribution of the study population, (2) the adequacy of sex-specific representation in each study using the participation/prevalence ratio, and (3) whether data were disaggregated by sex. The outcome was to determine whether recommendations for CPG s based on an assessment of the evidence should differ by sex. In total, 175 studies were included. The mean percentage of female participants reported in the studies was 24.5% ( SD : 6.6%; minimum: 0%; maximum: 51%). The mean participation/prevalence ratio was 0.62 ( SD : 0.16; minimum: 0.00; maximum: 1.19). Eighteen (10.2%) studies disaggregated the data by sex. Based on the participation/prevalence ratio and the sex-specific analyses presented, only 1 study provided adequate evidence to confidently inform the applicability of the CPG recommendations to male and female patients. Conclusions Implementing a systematic process for critically appraising sex-specific evidence for CPG s was straightforward and feasible. Inadequate enrollment and reporting by sex hindered comprehensive sex-specific assessment of the quality of evidence and strength of recommendations for a CPG on the management of ST-segment-elevation myocardial infarction.

Antimicrobial stewardship in rural nursing homes: Impact of interprofessional education and clinical decision tool implementation on urinary tract infection treatment in a cluster randomized trial.

OBJECTIVES: To measure the impact of an antimicrobial stewardship initiative on the rate of urine culture testing and antimicrobial prescribing for urinary tract infections (UTIs) between control and intervention sites. Secondary objectives included evaluation of potential harms of the intervention and identifying characteristics of the population prescribed antimicrobials for UTI. DESIGN: Cluster randomized controlled trial. SETTING: Nursing homes in rural Alberta, Canada. PARTICIPANTS: The study included 42 nursing homes ranging from 8 to 112 beds.Methods/interventions:Intervention sites received on-site staff education, physician academic detailing, and integrated clinical decision-making tools. Control sites provided standard care. Data were collected for 6 months prior to and 12 months after the intervention. RESULTS: Resident age (83.0 vs 83.8 years) and sex distribution (female, 62.5% vs 64.5%) were similar between the groups. Statistically significant decreases in the rate of urine culture testing (-2.1 tests per 1,000 resident days [RD]; 95% confidence interval [CI], -2.5 to -1.7; P < .001) and antimicrobial prescribing for UTIs (-0.7 prescriptions per 1,000 RD; 95% CI, -1.0 to -0.4; P < .001) were observed in the intervention group. There was no difference in hospital admissions (0.00 admissions per 1,000 RD; 95% CI, -0.4 to 0.3; P = .76), and the mortality rate decreased by 0.2 per 1,000 RD in the intervention group (95% CI, -0.5 to -0.1; P = .002). Chart reviews indicated that UTI symptoms were charted in 16% of cases and that urine culture testing occurred in 64.5% of cases. CONCLUSION: A multimodal antimicrobial stewardship intervention in rural nursing homes significantly decreased the rate of urine culture testing and antimicrobial prescriptions for UTI, with no increase in hospital admissions or mortality.

Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study.

We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition.

How ecological processes shape the outcomes of stock enhancement and harvest regulations in recreational fisheries.

Fish stocking and harvest regulations are frequently used to maintain or enhance freshwater recreational fisheries and contribute to fish conservation. However, their relative effectiveness has rarely been systematically evaluated using quantitative models that account for key size- and density-dependent ecological processes and adaptive responses of anglers. We present an integrated model of freshwater recreational fisheries where the population dynamics of two model species affect the effort dynamics of recreational anglers. With this model, we examined how stocking various fish densities and sizes (fry, fingerlings, and adults) performed relative to minimum-length limits using a variety of biological, social, and economic performance measures, while evaluating trade-offs. Four key findings are highlighted. First, stocking often augmented the exploited fish population, but size- and density-dependent bottlenecks limited the number of fry and fingerlings surviving to a catchable size in self-sustaining populations. The greatest enhancement of the catchable fish population occurred when large fish that escaped early bottlenecks were stocked, but this came at the cost of wild-stock replacement, thereby demonstrating a fundamental trade-off between fisheries benefits and conservation. Second, the relative performance of stocking naturally reproducing populations was largely independent of habitat quality and was generally low. Third, stocking was only economically advisable when natural reproduction was impaired or absent, stocking rates were low, and enough anglers benefitted from stocking to offset the associated costs. Fourth, in self-sustaining fish populations, minimum-length limits generally outperformed stocking when judged against a range of biological, social and economic objectives. By contrast, stocking in culture-based fisheries often generated substantial benefits. Collectively, our study demonstrates that size- and density-dependent processes, and broadly the degree of natural recruitment, drive the biological, social, and economic outcomes of popular management actions in recreational fisheries. To evaluate these outcomes and the resulting trade-offs, integrated fisheries-management models that explicitly consider the feedbacks among ecological and social processes are needed.

Drug Therapy for Abdominal Aortic Aneurysms Utilizing Omega-3 Unsaturated Fatty Acids and Their Derivatives.

BACKGROUND: Abdominal aortic aneurysms (AAA) are life-threatening because of the potential for rupture, resulting in death. The current standard treatment for AAA is surgery, comprising laparotomic graft replacement and endovascular repair. However, because surgery carries the risk of major complications and re-intervention, drug therapies are desirable because they may reduce the occurrence of enlargement and rupture. OBJECTIVE: Recent research shows that the progression of AAA is related to inflammatory reactions, especially those in the NF-κB pathway. Omega-3 polyunsaturated fatty acids (PUFA) show antiinflammatory effects. Some derivatives of omega-3 PUFA are known as specialized pro-resolving lipid mediators (SPM) such as resolvins. They play an important role in resolving inflammation. CONCLUSION: Omega-3 PUFA and SPM may show promised effects for drug treatment of AAA.

Targeted mitochondrial therapy using MitoQ shows equivalent renoprotection to angiotensin converting enzyme inhibition but no combined synergy in diabetes.

Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight. By the study end, both monotherapies improved renal function, decreasing glomerular hyperfiltration and albuminuria. All therapies prevented tubulointerstitial collagen deposition, but glomerular mesangial expansion was unaffected. Renal cortical concentrations of ATP, ADP, AMP, cAMP, creatinine phosphate and ATP:AMP ratio were increased by diabetes and mostly decreased with therapy. A higher creatine phosphate:ATP ratio in diabetic kidney cortices, suggested a decrease in ATP consumption. Diabetes elevated glucose 6-phosphate, fructose 6-phosphate and oxidised (NAD+ and NADP+) and reduced (NADH) nicotinamide dinucleotides, which therapy decreased generally. Diabetes increased mitochondrial oxygen consumption (OCR) at complex II-IV. MitoQ further increased OCR but decreased ATP, suggesting mitochondrial uncoupling as its mechanism of action. MitoQ showed renoprotection equivalent to ramipril but no synergistic benefits of combining these agents were shown.

Stably engineered nanobubbles and ultrasound - An effective platform for enhanced macromolecular delivery to representative cells of the retina.

Herein we showcase the potential of ultrasound-responsive nanobubbles in enhancing macromolecular permeation through layers of the retina, ultimately leading to significant and direct intracellular delivery; this being effectively demonstrated across three relevant and distinct retinal cell lines. Stably engineered nanobubbles of a highly homogenous and echogenic nature were fully characterised using dynamic light scattering, B-scan ultrasound and transmission electron microscopy (TEM). The nanobubbles appeared as spherical liposome-like structures under TEM, accompanied by an opaque luminal core and darkened corona around their periphery, with both features indicative of efficient gas entrapment and adsorption, respectively. A nanobubble +/- ultrasound sweeping study was conducted next, which determined the maximum tolerated dose for each cell line. Detection of underlying cellular stress was verified using the biomarker heat shock protein 70, measured before and after treatment with optimised ultrasound. Next, with safety to nanobubbles and optimised ultrasound demonstrated, each human or mouse-derived cell population was incubated with biotinylated rabbit-IgG in the presence and absence of ultrasound +/- nanobubbles. Intracellular delivery of antibody in each cell type was then quantified using Cy3-streptavidin. Nanobubbles and optimised ultrasound were found to be negligibly toxic across all cell lines tested. Macromolecular internalisation was achieved to significant, yet varying degrees in all three cell lines. The results of this study pave the way towards better understanding mechanisms underlying cellular responsiveness to ultrasound-triggered drug delivery in future ex vivo and in vivo models of the posterior eye.