Synthesis and Characterization of Temperature-Sensitive and Chemically Cross-Linked Poly(N-isopropylacrylamide)/Photosensitizer Hydrogels for Applications in Photodynamic Therapy

Copyright © 2018 American Chemical Society. A novel poly(N-isopropylacrylamide) (PNIPAM) hydrogel containing different photosensitizers (protoporphyrin IX (PpIX), pheophorbide a (Pba), and protoporphyrin IX dimethyl ester (PpIX-DME)) has been synthesized with a significant improvement in water solubility and potential for PDT applications compared to the individual photosensitizers (PSs). Conjugation of PpIX, Pba, and PpIX-DME to the poly(N-isopropylacrylamide) chain was achieved using the dispersion polymerization method. This study describes how the use of nanohydrogel structures to deliver a photosensitizer with low water solubility and high aggregation tendencies in polar solvents overcomes these limitations. FT-IR spectroscopy, UV-vis spectroscopy, 1 H NMR, fluorescence spectroscopy, SEM, and DLS analysis were used to characterize the PNIPAM-photosensitizer nanohydrogels. Spectroscopic studies indicate that the PpIX, Pba, and PpIX-DME photosensitizers are covalently conjugated to the polymer chains, which prevents aggregation and thus allows significant singlet oxygen production upon illumination. Likewise, the lower critical solution temperature was raised to ∼44 °C in the new PNIPAM-PS hydrogels. The PNIPAM hydrogels are biocompatible with > 90% cell viability even at high concentrations of the photosensitizer in vitro. Furthermore, a very sharp onset of light-dependent toxicity for the PpIX-based nanohydrogel in the nanomolar range and a more modest, but significant, photocytotoxic response for Pba-PNIPAM and PpIX-DME-PNIPAM nanohydrogels suggest that the new hydrogels have potential for applications in photodynamic therapy

Aran, Galway Bay and Slyne Head Nephrops Grounds (FU17) 2022 UWTV Survey Report and catch scenarios for 2023

This report provides the main results and findings of the 21st annual underwater television survey on the Aran, Galway Bay and Slyne head Nephrops grounds, ICES assessment area; Functional Unit 17. In 2022, due to disruption to the survey schedule caused by weather downtime, the UWTV survey could not complete the Aran Grounds and Slyne Head stations, and was only able to complete successfully the 5 Galway Bay stations. The survey was multi-disciplinary in nature collecting UWTV, CTD and other ecosystem data. The mean burrow density observed in Galway Bay, adjusted for edge effect, was 0.19 burrows/m2; and the final abundance estimate for this ground was 15 million burrows with a CV (Coefficient of Variance; relative standard error) of 3%. There were no sea-pen species nor trawl marks observed in the footage from Galway Bay. The 2022 UWTV survey was not deemed robust enough to derive fishing advice for 2023 owing to the reduced number of stations. As such, the stock size is considered unknown for 2022. Therefore, the assessment and catch advice for 2023 is based on the 2021 UWTV survey. The 2021 combined abundance estimate (331 million burrows) was below the MSY Btrigger reference (540 million burrows). Using the 2021 estimate of abundance and updated stock data imply that catches in 2023 should be no more than 363 tonnes, according to the EU MAP and ICES MSY approach and assuming that discard rates and fishery selection patterns do not change from the average of 2019–2021

Effects of Non-Aerobic Maximal Effort Exercise on Fatigue in Deconditioned Men and Women with Multiple Sclerosis

Multiple Sclerosis (MS) is a neurodegenerative disease of unknown etiology affecting women more frequently than men. Mental and physical fatigue complaints are often the most disabling symptoms for an MS patient. Both are multifactorial, potentially exacerbated by aerobic exercise, may prevent sustained physical functioning, and significantly interfere with activities of daily living1. A multi-center study was designed to investigate the effects of non-aerobic maximal effort exercise (MEE) for deconditioned persons with MS, with the expectation of minimizing fatigue. The IsoPUMP (Neuromuscular Engineering; Nashville, TN), is a specialized exercise and strength-sensing machine, designed to allow individuals to safely perform and record their non-aerobic MEE sessions. The Modified Fatigue Impact Scale (MFIS) and Multiple Sclerosis Functional Composite (MSFC) are common, accepted methods used to measure fatigue and function. The MFIS is a 21-item questionnaire which assesses the subjects’ perception of physical, cognitive, and psychosocial aspects of fatigue over a four-week period2. Each of the 21 items are scored on a scale from 0 (never) to 4 (almost always), and the total MFIS score is calculated by summing the circled number for each item. Total scores can range from 0 to 84; higher scores indicating a greater impact of fatigue on the person. The MFIS has three distinct subscales: (1) physical, (2) cognitive, and (3) psychosocial. These subscales can be scored independently by summing the questions that pertain to each subscale2. The MFIS physical subscale score can range from 0 – 36 and the MFIS cognitive subscale score can range from 0 – 40. The MSFC combines clinical measures used to assess lower limb function (Timed 25-Foot Walk [25-FW]), upper limb function (9-Hole Peg Test [9-HPT]), and cognition (Paced Auditory Serial Addition Test [PASAT-3”])3. The 25-FW is a quantitative measure of lower extremity function. The 9-HPT is a quantitative measure of arm and hand function where a subject inserts and then removes 9 pegs from a board, using one hand at a time. The time is recorded for each hand with the dominant hand trial first and the non-dominant hand trial second. The final score is recorded as the mean time for both hands. The PASAT-3” is a measure of cognitive function, specifically assessing auditory information processing speed, short-term memory, flexibility, and calculation ability. Cognitive dysfunction affects half of all MS patients; slowing ability to reason, concentrate, and recall5. In this test subjects listen to a series of 61 spoken numbers separated by 3 seconds and must add each number to the prior number. Their final PASAT-3” score is the number of correct additions in the series, with 60 reflecting a perfect score. The MSFC is then evaluated by creating Z-scores for each component, which compare each outcome with the average outcome of the study population. The three Z-scores are then averaged to create an overall composite score (the MSFC score) which represents change over time for that population of MS subjects3

Personalized Genetic Risk Counseling to Motivate Diabetes Prevention: A randomized trial

OBJECTIVE To examine whether diabetes genetic risk testing and counseling can improve diabetes prevention behaviors. RESEARCH DESIGN AND METHODS We conducted a randomized trial of diabetes genetic risk counseling among overweight patients at increased phenotypic risk for type 2 diabetes. Participants were randomly allocated to genetic testing versus no testing. Genetic risk was calculated by summing 36 single nucleotide polymorphisms associated with type 2 diabetes. Participants in the top and bottom score quartiles received individual genetic counseling before being enrolled with untested control participants in a 12-week, validated, diabetes prevention program. Middle-risk quartile participants were not studied further. We examined the effect of this genetic counseling intervention on patient self-reported attitudes, program attendance, and weight loss, separately comparing higher-risk and lower-risk result recipients with control participants. RESULTS The 108 participants enrolled in the diabetes prevention program included 42 participants at higher diabetes genetic risk, 32 at lower diabetes genetic risk, and 34 untested control subjects. Mean age was 57.9 ± 10.6 years, 61% were men, and average BMI was 34.8 kg/m2, with no differences among randomization groups. Participants attended 6.8 ± 4.3 group sessions and lost 8.5 ± 10.1 pounds, with 33 of 108 (30.6%) losing ≥5% body weight. There were few statistically significant differences in self-reported motivation, program attendance, or mean weight loss when higher-risk recipients and lower-risk recipients were compared with control subjects (P > 0.05 for all but one comparison). CONCLUSIONS Diabetes genetic risk counseling with currently available variants does not significantly alter self-reported motivation or prevention program adherence for overweight individuals at risk for diabetes

FU19 Nephrops Grounds 2022 UWTV Survey Report and catch scenarios for 2023

This report provides the main results of the twelfth underwater television survey of the various Nephrops patches in Functional Unit 19. The survey was multi-disciplinary in nature collecting UWTV and other ecosystem data. In 2022 a total 42 UWTV stations were successfully completed. The mean density estimates varied considerably across the different patches. The 2022 raised abundance estimate showed a 4% decrease from the 2021 estimate and at 259 million burrows is below the MSY Btrigger reference point (430 million). Using the 2022 estimate of abundance and updated stock data implies catch in 2023 that correspond to the F ranges in the EU multi annual plan for Western Waters are between 302 and 338 tonnes (assuming that discard rates and fishery selection patterns do not change from the average of 2019–2021). One species of sea pen was observed; Virgularia mirabilis which has been observed on previous surveys of FU19. Trawl marks were observed at 12% of the stations surveyed

The Labadie, Jones and Cockburn Banks Nephrops Grounds (FU2021) 2022 UWTV Survey Report and catch scenarios for 2023

This report is embargoed unti the 1st November when it will be published in sync with ICES.This report provides the main results of the 2022 underwater television survey on the ‘Labadie, Jones and Cockburn Banks’ ICES assessment area; Functional Unit 2021. The 2022 annual survey was multi-disciplinary in nature collecting UWTV and other ecosystem data. A total of 92 UWTV stations were completed at 6 nm intervals over a randomised isometric grid design. The mean burrow density was 0.10 burrows/m2 compared with 0.12 burrows/m2 in the year 2021. The 2022 geostatistical abundance estimate was 1032 million, a 14% decrease on the abundance from 2021, with a CV of 5%, which is well below the upper limit of 20% recommended by SGNEPS 2012. Low to medium densities were observed throughout the ground. Using the 2022 estimate of abundance and updated stock data implies catch in 2023 that correspond to the ICES MSY approach of 1803 tonnes assuming that discard rates and fishery selection patterns do not change from the average of 2019–2021. One species of sea-pen (Virgularia mirabilis) was recorded as present at the stations surveyed. Trawl marks were observed at 20% of the stations surveyed

Identifying the science and technology dimensions of emerging public policy issues through horizon scanning

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security

Can modeling of HIV treatment processes improve outcomes? Capitalizing on an operations research approach to the global pandemic

<p>Abstract</p> <p>Background</p> <p>Mathematical modeling has been applied to a range of policy-level decisions on resource allocation for HIV care and treatment. We describe the application of classic operations research (OR) techniques to address logistical and resource management challenges in HIV treatment scale-up activities in resource-limited countries.</p> <p>Methods</p> <p>We review and categorize several of the major logistical and operational problems encountered over the last decade in the global scale-up of HIV care and antiretroviral treatment for people with AIDS. While there are unique features of HIV care and treatment that pose significant challenges to effective modeling and service improvement, we identify several analogous OR-based solutions that have been developed in the service, industrial, and health sectors.</p> <p>Results</p> <p>HIV treatment scale-up includes many processes that are amenable to mathematical and simulation modeling, including forecasting future demand for services; locating and sizing facilities for maximal efficiency; and determining optimal staffing levels at clinical centers. Optimization of clinical and logistical processes through modeling may improve outcomes, but successful OR-based interventions will require contextualization of response strategies, including appreciation of both existing health care systems and limitations in local health workforces.</p> <p>Conclusion</p> <p>The modeling techniques developed in the engineering field of operations research have wide potential application to the variety of logistical problems encountered in HIV treatment scale-up in resource-limited settings. Increasing the number of cross-disciplinary collaborations between engineering and public health will help speed the appropriate development and application of these tools.</p

The first whole genome and transcriptome of the cinereous vulture reveals adaptation in the gastric and immune defense systems and possible convergent evolution between the Old and New World vultures

Background: The cinereous vulture, Aegypius monachus, is the largest bird of prey and plays a key role in the ecosystem by removing carcasses, thus preventing the spread of diseases. Its feeding habits force it to cope with constant exposure to pathogens, making this species an interesting target for discovering functionally selected genetic variants. Furthermore, the presence of two independently evolved vulture groups, Old World and New World vultures, provides a natural experiment in which to investigate convergent evolution due to obligate scavenging. Results: We sequenced the genome of a cinereous vulture, and mapped it to the bald eagle reference genome, a close relative with a divergence time of 18 million years. By comparing the cinereous vulture to other avian genomes, we find positively selected genetic variations in this species associated with respiration, likely linked to their ability of immune defense responses and gastric acid secretion, consistent with their ability to digest carcasses. Comparisons between the Old World and New World vulture groups suggest convergent gene evolution. We assemble the cinereous vulture blood transcriptome from a second individual, and annotate genes. Finally, we infer the demographic history of the cinereous vulture which shows marked fluctuations in effective population size during the late Pleistocene. Conclusions: We present the first genome and transcriptome analyses of the cinereous vulture compared to other avian genomes and transcriptomes, revealing genetic signatures of dietary and environmental adaptations accompanied by possible convergent evolution between the Old World and New World vulturesopen

Current quality of life and its determinants among opiate-dependent individuals five years after starting methadone treatment

This study explores the current QoL of opiate-dependent individuals who started outpatient methadone treatment at least 5 years ago and assesses the influence of demographic, psychosocial, drug and health-related variables on individuals' QoL. Participants (n = 159) were interviewed about their current QoL, psychological distress and severity of drug-related problems, using the Lancashire Quality of Life Profile, the Brief Symptom Inventory and the Addiction Severity Index. Potential determinants of QoL were assessed in a multiple linear regression analysis. Five years after the start of methadone treatment, opiate-dependent individuals report low QoL scores on various domains. No association was found between drug-related variables and QoL, but a significant negative impact of psychological distress was identified. Severity of psychological distress, taking medication for psychological problems and the inability to change one's living situation were associated with lower QoL. Having at least one good friend and a structured daily activity had a significant, positive impact on QoL. Opiate-dependent individuals' QoL is mainly determined by their psychological well-being and a number of psychosocial variables. These findings highlight the importance of a holistic approach to treatment and support in methadone maintenance treatment, which goes beyond fixing the negative physical consequences of opiate dependence