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Research has found that helping others facilitates well-being for Indigenous peoples living with HIV and AIDS, but limited research exists that investigates the mechanism(s) underlying this relationship. Indigenous perspectives posit that helping others facilitates well-being through the development of an individual's spiritual, physical, emotional, and mental aspects (four aspects). Similarly, self-determination theory posits that helping others facilitates well-being by satisfying basic psychological needs. In the present study, we examined if helping others facilitates well-being through the fulfillment of the spiritual, physical, emotional, and mental aspects among Indigenous peoples living with HIV and AIDS. We used a convergent parallel mixed methods design, coupled with a community-engaged approach grounded in the United Nations Greater Involvement of People Living with HIV and AIDS principles and Indigenous and decolonizing research methodologies. Survey (n = 117) and interview data (n = 9) collected by an Indigenous-led HIV/AIDS organization in Canada were employed to examine the relationship between helping, the four aspects, and well-being. Participants were primarily First Nations leaders and mentors who live with HIV/AIDS, with some Métis and Inuit. A parallel multiple mediation model and reflexive thematic analysis were used to analyze the relationship between helping, the four aspects, and well-being. Mixed-methods findings support the idea that helping others promotes well-being by fulfilling the emotional and mental aspects. Qualitative findings demonstrated this relationship for all four aspects. This research may facilitate the development of programs to support Indigenous peoples living with HIV/AIDS well-being and contribute to the literature on integrating Indigenous perspectives and methodologies within psychological research.
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We report developmental details of a high-sensitivity Stark absorption spectrometer featuring a laser-driven light source. The light source exhibits intensity fluctuations of â¼0.3% over timescales ranging from 1 min to 12 h, minimal drift (≤0.1%/h), and very little 1/f noise at frequencies greater than 200 Hz, which are comparable to or better than an arc-driven light source. Additional features of the spectrometer include balanced detection with multiplex sampling, which yielded lower noise in A, and constant wavelength or wavenumber (energy) spectral bandpass modes. We achieve noise amplitudes of â¼7 × 10-4 and â¼6 × 10-6 in measurements of single A and ΔA spectra (with 92 data points) taking â¼7 and â¼19 min, respectively.
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We review comprehensive observations of electromagnetic ion cyclotron (EMIC) wave-driven energetic electron precipitation using data collected by the energetic electron detector on the Electron Losses and Fields InvestigatioN (ELFIN) mission, two polar-orbiting low-altitude spinning CubeSats, measuring 50-5000 keV electrons with good pitch-angle and energy resolution. EMIC wave-driven precipitation exhibits a distinct signature in energy-spectrograms of the precipitating-to-trapped flux ratio: peaks at >0.5 MeV which are abrupt (bursty) (lasting â¼17 s, or ΔLâ¼0.56) with significant substructure (occasionally down to sub-second timescale). We attribute the bursty nature of the precipitation to the spatial extent and structuredness of the wave field at the equator. Multiple ELFIN passes over the same MLT sector allow us to study the spatial and temporal evolution of the EMIC wave - electron interaction region. Case studies employing conjugate ground-based or equatorial observations of the EMIC waves reveal that the energy of moderate and strong precipitation at ELFIN approximately agrees with theoretical expectations for cyclotron resonant interactions in a cold plasma. Using multiple years of ELFIN data uniformly distributed in local time, we assemble a statistical database of â¼50 events of strong EMIC wave-driven precipitation. Most reside at Lâ¼5-7 at dusk, while a smaller subset exists at Lâ¼8-12 at post-midnight. The energies of the peak-precipitation ratio and of the half-peak precipitation ratio (our proxy for the minimum resonance energy) exhibit an L-shell dependence in good agreement with theoretical estimates based on prior statistical observations of EMIC wave power spectra. The precipitation ratio's spectral shape for the most intense events has an exponential falloff away from the peak (i.e., on either side of â¼1.45 MeV). It too agrees well with quasi-linear diffusion theory based on prior statistics of wave spectra. It should be noted though that this diffusive treatment likely includes effects from nonlinear resonant interactions (especially at high energies) and nonresonant effects from sharp wave packet edges (at low energies). Sub-MeV electron precipitation observed concurrently with strong EMIC wave-driven >1 MeV precipitation has a spectral shape that is consistent with efficient pitch-angle scattering down to â¼ 200-300 keV by much less intense higher frequency EMIC waves at dusk (where such waves are most frequent). At â¼100 keV, whistler-mode chorus may be implicated in concurrent precipitation. These results confirm the critical role of EMIC waves in driving relativistic electron losses. Nonlinear effects may abound and require further investigation.
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Hydrogen selenide (H2Se) is a possible bioregulator, potential gasotransmitter, and important precursor in biological organoselenium compound synthesis. Early tools for H2Se research have benefitted from available mechanistic understanding of analogous small molecules developed for detecting or delivering H2S. A now common approach for H2S delivery is the use of small molecule thiocarbamates that can be engineered to release COS, which is quickly converted to H2S by carbonic anhydrase. To expand our understanding of the chemical underpinnings that enable H2Se delivery, we investigated whether selenocarbamates undergo similar chemistry to release carbonyl selenide (COSe). Using both light- and hydrolysis-activated systems, we demonstrate that unlike their lighter thiocarbamate congeners, selenocarbamates release H2Se directly with concomitant isocyanate formation rather than by the intermediate release of COSe. This reaction mechanism for direct H2Se release is further supported by computational investigations that identify a ΔΔG â¼ 25 kcal mol-1 between the H2Se and COSe release pathways in the absence of protic solvent. This work highlights fundamentally new approaches for H2Se release from small molecules and advances the understanding of reactivity differences between reactive sulfur and selenium species.
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CONTEXT: Medical students with no previous experience may find it difficult to identify and palpate bony landmarks while learning physical examination skills. In a study of 168 medical schools, 72.6â¯% have indicated that they are utilizing ultrasound in their curriculum. Although the integration of ultrasound curriculum has become more widespread, the depth of instruction is inconsistent. Ultrasound is not commonly taught in conjunction with palpation of bony landmarks in osteopathic structural examination. OBJECTIVES: The objective of this analysis was to identify whether utilizing ultrasound assistance in teaching palpation of specific thoracic vertebral bony landmarks would improve palpation accuracy in first-year medical students with no previous palpatory experience. METHODS: First-year medical students were given video instructions to palpate and identify a thoracic vertebral transverse process and to mark it with invisible ink. The participants were then taught and instructed to utilize ultrasound to identify the same landmark and mark it with a different color. The accuracy of palpation was measured with digital calipers. RESULTS: A test of the overall hypothesis that participants will show improved accuracy utilizing ultrasound compared with hand palpation was not significant (F=0.76, p>0.05). When separating students into groups according to patient body mass index (BMI), however, there was a trend toward significance (F=2.90, p=0.071) for an interaction effect between patient BMI and the repeated measures variable of palpation/ultrasound. When looking specifically at only those participants working with a normal BMI patient, there was a significant improvement in their accuracy with the use of ultrasound (F=7.92, p=0.017). CONCLUSIONS: The analysis found increased accuracy in bony landmark identification in untrained palpators utilizing ultrasound vs. palpation alone in a normal BMI model, but not in obese or overweight BMI models. This study shows promise to the value that ultrasound may have in medical education, especially with respect to early palpation training and landmark identification.
Subject(s)
Palpation , Students, Medical , Humans , Palpation/methods , Ultrasonography/methods , Physical Examination , CurriculumABSTRACT
Glaucomatous neurodegeneration, a blinding disease affecting millions worldwide, has a need for the exploration of new and effective therapies. Previously, the glucagon-like peptide-1 receptor (GLP-1R) agonist NLY01 was shown to reduce microglia/macrophage activation, rescuing retinal ganglion cells after IOP elevation in an animal model of glaucoma. GLP-1R agonist use is also associated with a reduced risk for glaucoma in patients with diabetes. In this study, we demonstrate that several commercially available GLP-1R agonists, administered either systemically or topically, hold protective potential in a mouse model of hypertensive glaucoma. Further, the resulting neuroprotection likely occurs through the same pathways previously shown for NLY01. This work contributes to a growing body of evidence suggesting that GLP-1R agonists represent a viable therapeutic option for glaucoma.
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A detailed overview of the knowledge gaps in our understanding of the heliospheric interaction with the largely unexplored Very Local Interstellar Medium (VLISM) are provided along with predictions of with the scientific discoveries that await. The new measurements required to make progress in this expanding frontier of space physics are discussed and include in-situ plasma and pick-up ion measurements throughout the heliosheath, direct sampling of the VLISM properties such as elemental and isotopic composition, densities, flows, and temperatures of neutral gas, dust and plasma, and remote energetic neutral atom (ENA) and Lyman-alpha (LYA) imaging from vantage points that can uniquely discern the heliospheric shape and bring new information on the interaction with interstellar hydrogen. The implementation of a pragmatic Interstellar Probe mission with a nominal design life to reach 375 Astronomical Units (au) with likely operation out to 550 au are reported as a result of a 4-year NASA funded mission study.
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PURPOSE: To determine baseline patient characteristics that predict the need for glaucoma surgery or blindness in eyes with neovascular glaucoma (NVG) despite intravitreal antivascular endothelial growth factor therapy. METHODS: This is a retrospective cohort study of patients with NVG who had not previously received glaucoma surgery and were treated with intravitreal antivascular endothelial growth factor injections at the time of diagnosis, from September 8, 2011, to May 8, 2020, at a large, retina subspecialty practice. RESULTS: Of 301 newly presenting NVG eyes, 31% required glaucoma surgery and 20% progressed to no light perception vision despite treatment. Patients with intraocular pressure >35 mmHg ( P < 0.001), two or more topical glaucoma medications ( P = 0.003), worse than 20/100 vision ( P = 0.024), proliferative diabetic retinopathy ( P = 0.001), eye pain or discomfort ( P = 0.010), and new patient status ( P = 0.015) at the time of NVG diagnosis were at a higher risk of glaucoma surgery or blindness regardless of antivascular endothelial growth factor therapy. The effect of panretinal photocoagulation was not statistically significant in a subgroup analysis of patients without media opacity ( P = 0.199). CONCLUSION: Several baseline characteristics at the time of presentation to a retina specialist with NVG seem to portend a higher risk of uncontrolled glaucoma despite the use of antivascular endothelial growth factor therapy. Prompt referral of these patients to a glaucoma specialist should be strongly considered.
Subject(s)
Glaucoma, Neovascular , Glaucoma , Humans , Bevacizumab/therapeutic use , Glaucoma, Neovascular/drug therapy , Glaucoma, Neovascular/etiology , Angiogenesis Inhibitors , Endothelial Growth Factors , Vascular Endothelial Growth Factor A , Retrospective Studies , Retina , Intraocular Pressure , Intravitreal Injections , Blindness/etiology , Risk FactorsABSTRACT
PURPOSE OF REVIEW: The aim of this study was to update visual outcomes, microbial spectrum and complications in eyes with endophthalmitis following cataract surgery. RECENT FINDINGS: A single-institution, retrospective review of eyes treated for endophthalmitis following cataract surgery between 2 January 2014 and 10 January 2017. This study included 112 cases of endophthalmitis following cataract surgery, 58 of which were culture-positive (51.8%). The most isolated organisms were coagulase-negative Staphylococci (56.9%). Oral flora were present in 17.2% of cases. At 6 months, 71.7% of patients achieved visual acuity of at least 20/200 and 51.7% achieved at least 20/40 or better. Visual acuity was better in culture-negative vs. culture-positive cases (â¼20/290 vs. â¼20/80, P â = â0.03), and in nonoral flora-associated vs. oral flora-associated culture-positive cases (â¼CF vs. â¼20/150, P â < â0.01). SUMMARY: Following postcataract surgery endophthalmitis, approximately 70% of eyes achieved vision of 20/200 or better and half achieved vision of 20/40 or better 6âmonths after treatment. Poor visual outcomes were seen in eyes with positive bacterial cultures and with oral flora.
Subject(s)
Cataract Extraction , Cataract , Endophthalmitis , Eye Infections, Bacterial , Humans , Eye Infections, Bacterial/diagnosis , Eye Infections, Bacterial/etiology , Eye Infections, Bacterial/drug therapy , Postoperative Complications , Endophthalmitis/etiology , Cataract Extraction/adverse effects , Bacteria , Retrospective Studies , Anti-Bacterial Agents/therapeutic useABSTRACT
The number of studies using skeletal muscle (SkM) cell culture models to study exercise in vitro are rapidly expanding. Progressively, more comprehensive analysis methods, such as different omics approaches including transcriptomics, proteomics, and metabolomics have been used to examine the intra- and extracellular molecular responses to exercise mimicking stimuli in cultured myotubes. Among other techniques, exercise-like electrical pulse stimulation (EL-EPS) and mechanical stretch of SkM cells are the two most commonly used methods to mimic exercise in vitro. In this mini-review, we focus on these two approaches and their effects on the omics of myotubes and/or cell culture media. Furthermore, besides traditional two-dimensional (2-D) methods, the use of three-dimensional (3-D) SkM approaches are increasing in the field of in vitro exercise mimicry. Our aim with this mini-review is to provide the reader with an up-to-date overview of the 2-D and 3-D models and the use of omics approaches to study the molecular response to exercise in vitro.
Subject(s)
Muscle Fibers, Skeletal , Muscle, Skeletal , Muscle, Skeletal/physiology , Muscle Fibers, Skeletal/physiology , Exercise/physiology , Electric StimulationABSTRACT
Reactive oxygen species (ROS) are important modulators of physiological signaling and play important roles in bone tissue regulation. Both reactive sulfur species (RSS) and reactive selenium species (RSeS) are involved in ROS signaling, and recent work suggests RSS and RSeS involvement in the regulation of bone homeostasis. For example, RSS can promote osteogenic differentiation and decrease osteoclast activity and differentiation, and the antioxidant activity of RSeS play crucial roles in balancing bone remodeling. Here, we outline current research progress on the application of RSS and RSeS in bone disease and regeneration. Focusing on these investigations, we highlight different methods, tools, and sources of RSS and RSeS, and we also highlight future opportunities for delivery of RSS and RSeS in biological environments relating to bone.
Subject(s)
Selenium , Bone and Bones , Homeostasis , Osteogenesis , Reactive Oxygen Species , SulfurABSTRACT
OBJECTIVE: To understand community seroprevalence of SARS-CoV-2 in children and adolescents. This is vital to understanding the susceptibility of this cohort to COVID-19 and to inform public health policy for disease control such as immunisation. DESIGN: We conducted a community-based cross-sectional seroprevalence study in participants aged 0-18 years old recruiting from seven regions in England between October 2019 and June 2021 and collecting extensive demographic and symptom data. Serum samples were tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins using Roche assays processed at UK Health Security Agency laboratories. Prevalence estimates were calculated for six time periods and were standardised by age group, ethnicity and National Health Service region. RESULTS: Post-first wave (June-August 2020), the (anti-spike IgG) adjusted seroprevalence was 5.2%, varying from 0.9% (participants 10-14 years old) to 9.5% (participants 5-9 years old). By April-June 2021, this had increased to 19.9%, varying from 13.9% (participants 0-4 years old) to 32.7% (participants 15-18 years old). Minority ethnic groups had higher risk of SARS-CoV-2 seropositivity than white participants (OR 1.4, 95% CI 1.0 to 2.0), after adjusting for sex, age, region, time period, deprivation and urban/rural geography. In children <10 years, there were no symptoms or symptom clusters that reliably predicted seropositivity. Overall, 48% of seropositive participants with complete questionnaire data recalled no symptoms between February 2020 and their study visit. CONCLUSIONS: Approximately one-third of participants aged 15-18 years old had evidence of antibodies against SARS-CoV-2 prior to the introduction of widespread vaccination. These data demonstrate that ethnic background is independently associated with risk of SARS-CoV-2 infection in children. TRIAL REGISTRATION NUMBER: NCT04061382.
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Large-scale disturbances generated by the Sun's dynamics first propagate through the heliosphere, influence the heliosphere's outer boundaries, and then traverse and modify the very local interstellar medium (VLISM). The existence of shocks in the VLISM was initially suggested by Voyager observations of the 2-3 kHz radio emissions in the heliosphere. A couple of decades later, both Voyagers crossed the definitive edge of our heliosphere and became the first ever spacecraft to sample interstellar space. Since Voyager 1's entrance into the VLISM, it sampled electron plasma oscillation events that indirectly measure the medium's density, increasing as it moves further away from the heliopause. Some of the observed electron oscillation events in the VLISM were associated with the local heliospheric shock waves. The observed VLISM shocks were very different than heliospheric shocks. They were very weak and broad, and the usual dissipation via wave-particle interactions could not explain their structure. Estimates of the dissipation associated with the collisionality show that collisions can determine the VLISM shock structure. According to theory and models, the existence of a bow shock or wave in front of our heliosphere is still an open question as there are no direct observations yet. This paper reviews the outstanding observations recently made by the Voyager 1 and 2 spacecraft, and our current understanding of the properties of shocks/waves in the VLISM. We present some of the most exciting open questions related to the VLISM and shock waves that should be addressed in the future.
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PURPOSE: To evaluate the effect of loss to follow-up (LTFU) on outcomes in eyes with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (VEGF). DESIGN: Retrospective cohort study. METHODS: Single-center study of 90 eyes of 73 patients with nonproliferative diabetic retinopathy (NPDR) and DME treated with anti-VEGF injections who were LTFU for >6 months. Main outcomes were the change in mean visual acuity (VA) and central foveal thickness at the return and final visits compared with the visit before LTFU. RESULTS: The mean age was 64.5 years, the mean LTFU duration was 322 days, and the mean follow-up duration after return was 502 days. Compared with the mean VA at the visit before LTFU (0.42, Snellen â¼20/52), mean VA worsened at the return visit (0.54, Snellen â¼20/69, P = .004). No significant change in the mean VA was noted at the 3-month after return visit (0.50, Snellen â¼20/63), the 6-month after return visit (0.46, Snellen â¼20/57), the 12-month after return visit (0.42, Snellen â¼20/52), or the final follow-up (0.47, Snellen â¼20/59). When analyzed by NPDR severity before LTFU, no difference in VA was found from the visit before LTFU to the final visit. Mean central foveal thickness increased when comparing the visit before LTFU (270 µm) with the return visit (305 µm, P = .012), but no difference was found by the final visit (247 µm, P = .07). CONCLUSIONS: Anti-VEGF-treated patients with DME who were LTFU for a prolonged period experienced a modest decline in VA that recovered after restarting treatment.
Subject(s)
Angiogenesis Inhibitors , Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/drug therapy , Humans , Intravitreal Injections , Lost to Follow-Up , Macular Edema/diagnosis , Macular Edema/drug therapy , Macular Edema/etiology , Middle Aged , Retrospective Studies , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
BACKGROUND: Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of â¼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 (32P) microparticles, combined with standard-of-care chemotherapy. PATIENTS AND METHODS: In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks. RESULTS: Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively. CONCLUSIONS: Endoscopic ultrasound-guided 32P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adult , Albumins , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Humans , Irinotecan/pharmacology , Irinotecan/therapeutic use , Leucovorin/pharmacology , Leucovorin/therapeutic use , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , Paclitaxel , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Pilot Projects , GemcitabineABSTRACT
BACKGROUND: This study describes the epidemiology of COVID-19 outbreaks in four care homes in terms of spread, severity, presentation and interventions. METHODS: Participants were 100 residents and 102 staff from four co-located care homes in Wales. Data were collected from the homes and Public Health Wales, including demographics, presentations, test status and results, hospital admissions and deaths. Genomic sequencing of confirmed case samples was completed, where possible. Epi-curves, crude attack rates, a Kaplan-Meier survival curve and adjusted hazard ratios were calculated using R. RESULTS: About 14 confirmed and 43 possible resident cases, 23 confirmed and 47 possible staff cases occurred. Crude attack rates of possible and confirmed cases were 57% (residents) and 69% (staff). Genomic sequencing for 10 confirmed case PCR samples identified at least 5 different UK lineages of COVID-19.42 (42%) residents died, 23 (55%) with COVID-19 or suspected COVID-19 recorded on the death certificate. The hazard ratio for death amongst resident possible and confirmed cases compared to null cases, adjusting for age and sex, was 13.26 (95% CI 5.61-31.34). CONCLUSIONS: There were extensive outbreaks of COVID-19 in these homes with high crude attack rates and deaths. Universal testing and early isolation of residents are recommended.
Subject(s)
COVID-19 , COVID-19/epidemiology , Disease Outbreaks , Humans , Nursing Homes , Retrospective Studies , Wales/epidemiologyABSTRACT
Retinal inflammation underlies multiple prevalent ocular and neurological diseases. Similar inflammatory processes are observed in glaucomatous optic neuropathy, age-related macular degeneration, retinitis pigmentosa, posterior uveitis, Alzheimer's disease, and Parkinson's disease. In particular, human and animal studies have demonstrated the important role microglia/macrophages play in initiating and maintaining a pro-inflammatory environment in degenerative processes impacting vision. On the other hand, microglia have also been shown to have a protective role in multiple central nervous system diseases. Identifying the mechanisms underlying cell dysfunction and death is the first step toward developing novel therapeutics for these diseases impacting the central nervous system. In addition to reviewing recent key studies defining important mediators of retinal inflammation, with an emphasis on translational studies that bridge this research from bench to bedside, we also highlight a promising therapeutic class of medications, the glucagon-like peptide-1 receptor agonists. Finally, we propose areas where additional research is necessary to identify mechanisms that can be modulated to shift the balance from a neurotoxic to a neuroprotective retinal environment.
Subject(s)
Neurodegenerative Diseases , Retinitis Pigmentosa , Animals , Brain/metabolism , Inflammation/metabolism , Microglia/metabolism , Myeloid Cells/metabolism , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Retina/metabolism , Retinitis Pigmentosa/metabolismABSTRACT
Measurements from NASA's Van Allen Probes have transformed our understanding of the dynamics of Earth's geomagnetically-trapped, charged particle radiation. The Van Allen Probes were equipped with the Magnetic Electron Ion Spectrometers (MagEIS) that measured energetic and relativistic electrons, along with energetic ions, in the radiation belts. Accurate and routine measurement of these particles was of fundamental importance towards achieving the scientific goals of the mission. We provide a comprehensive review of the MagEIS suite's on-orbit performance, operation, and data products, along with a summary of scientific results. The purpose of this review is to serve as a complement to the MagEIS instrument paper, which was largely completed before flight and thus focused on pre-flight design and performance characteristics. As is the case with all space-borne instrumentation, the anticipated sensor performance was found to be different once on orbit. Our intention is to provide sufficient detail on the MagEIS instruments so that future generations of researchers can understand the subtleties of the sensors, profit from these unique measurements, and continue to unlock the mysteries of the near-Earth space radiation environment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11214-021-00855-2.
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Hydrogen selenide (H2Se) is a central metabolite in the biological processing of selenium for incorporation into selenoproteins, which play crucial antioxidant roles in biological systems. Despite being integral to proper physiological function, this reactive selenium species (RSeS) has received limited attention. We recently reported an early example of a H2Se donor (TDN1042) that exhibited slow, sustained release through hydrolysis. Here we expand that technology based on the PâSe motif to develop cyclic-PSe compounds with increased rates of hydrolysis and function through well-defined mechanisms as monitored by 31P and 77Se NMR spectroscopy. In addition, we report a colorimetric method based on the reaction of H2Se with NBD-Cl to generate NBD-SeH (λmax = 551 nm), which can be used to detect free H2Se. Furthermore, we use TOF-SIMS (time of flight secondary ion mass spectroscopy) to demonstrate that these H2Se donors are cell permeable and use this technique for spatial mapping of the intracellular Se content after H2Se delivery. Moreover, these H2Se donors reduce endogenous intracellular reactive oxygen species (ROS) levels. Taken together, this work expands the toolbox of H2Se donor technology and sets the stage for future work focused on the biological activity and beneficial applications of H2Se and related bioinorganic RSeS.