Lens epithelial cell proliferation and differentiation are naturally well regulated and controlled, a characteristic essential for lens structure, symmetry and function. The effect of ionizing ...radiation on lens epithelial cell proliferation has been demonstrated in previous studies at high acute doses, but the effect of dose and dose rate on proliferation has not yet been considered. In this work, mice received single acute doses of 0.5, 1 and 2 Gy of radiation, at dose rates of 0.063 and 0.3 Gy/min. Eye lenses were isolated postirradiation at 30 min up until 14 days and flat-mounted. Then, cell proliferation rates were determined using biomarker Ki67. As expected, radiation increased cell proliferation 2 and 24 h postirradiation transiently (undetectable 14 days postirradiation) and was dose dependent (changes were very significant at 2 Gy; P = 0.008). A dose-rate effect did not reach significance in this study (P = 0.054). However, dose rate and lens epithelial cell region showed significant interactions (P < 0.001). These observations further our mechanistic understanding of how the lens responds to radiation.
To improve our understanding of pattern formation during development and disease we heavily rely on the identification of novel regulators and pathways. While RNA sequencing yields genome-wide ...expression data that suit this purpose, it lacks spatial resolution. Such spatial resolution can be obtained by microscopy-based methods like in situ hybridization, but these fail to provide information on more than a few genes at a time. Here, we describe tomo-seq, a technique that combines the advantages of the above-mentioned approaches and provides genome-wide expression data with spatial information. The tomo-seq technique is based on cryosectioning of an embryo or tissue of interest and performing RNA-seq on individual sections. Using this method, we have generated genome-wide transcriptomics with high spatial resolution of the whole zebrafish embryo at various stages of development (Junker et al., 2014) and of adult zebrafish hearts after injury (Wu et al., 2016).
The Environment and Headache: a Narrative Review Elser, Holly; Kruse, Caroline F. G.; Schwartz, Brian S. ...
Current environmental health reports,
06/2024, Volume:
11, Issue:
2
Journal Article
Peer reviewed
Purpose of Review
In this narrative review, we summarize the peer-reviewed literature published between 2017 and 2022 that evaluated ambient environmental risk factors for primary headache disorders, ...which affect more than half of the population globally. Primary headache disorders include migraine, tension-type headache (TTH), and trigeminal and autonomic cephalalgias (TAC).
Recent findings
We identified 17 articles that met the inclusion criteria via PubMed or Google Scholar. Seven studies (41%) relied on data from US populations. The remaining studies were conducted in China, Taiwan, Germany, Ghana, Japan, the Netherlands, South Korea, and Turkey. Air pollution was the most frequently assessed environmental risk factor. Most studies were cross-sectional and focused on all-cause or migraine headaches; one study included TTH, and none included TAC. Short-term exposure to fine particulate matter (PM2.5) was not consistently associated with headache endpoints, but long-term exposure to PM2.5 was associated with migraine headache prevalence and severity across multiple studies. Elevated ambient temperature, changes in weather, oil and gas well exposure, and less natural greenspace, but not noise pollution, were also associated with headache. No studies considered water pollution, metal exposure, ultrafine particulate matter, or wildfire smoke exposure.
Summary
There is a need for ongoing research focused on headache and the environment. Study designs with the greatest explanatory power may include longitudinal studies that capture the episodic nature of headache and case-crossover analysis, which control for time-invariant individual-level confounders by design. There is also a clear need for research that considers comorbid psychiatric illness and socioeconomic position as powerful modifiers of the effect of the environment on headache.
This review provides a comprehensive analysis of the structure, neurochemical content, and functions of corneal nerves, with special emphasis on human corneal nerves. A revised interpretation of ...human corneal nerve architecture is presented based on recent observations obtained by in vivo confocal microscopy (IVCM), immunohistochemistry, and ultrastructural analyses of serial-sectioned human corneas. Current data on the neurotransmitter and neuropeptide contents of corneal nerves are discussed, as are the mechanisms by which corneal neurochemicals and associated neurotrophins modulate corneal physiology, homeostasis and wound healing. The results of recent clinical studies of topically applied neuropeptides and neurotrophins to treat neurotrophic keratitis are reviewed. Recommendations for using IVCM to evaluate corneal nerves in health and disease are presented.
A specialized microenvironment or niche, which regulates maintenance, self-renewal, activation, and proliferation of stem cells by external signals, is one of the key prerequisites for stem cell ...function. However, the parameters determining the limbal stem cell niche are not yet defined. In order to characterize the role of basement membrane (BM) and extracellular matrix components in the generation of a microenvironmental niche for limbal stem and progenitor cells, we extensively analyzed the topographical variations of the BM zone of human ocular surface epithelia using immunohistochemistry and a large panel of antibodies to most of the presently described intrinsic and associated BM components. Apart from BM components uniformly expressed throughout all ocular surface epithelia (e.g. type IV collagen α5 and α6 chains, collagen types VII, XV, XVII, and XVIII, laminin-111, laminin-332, laminin chains α3, β3,and γ2, fibronectin, matrilin-2 and -4, and perlecan), the BM of the limbal epithelium shared many similarities with that of the conjunctival epithelium, including positive labelling for type IV collagen α1 and α2 chains, laminin α5, β2, and γ1 chains, nidogen-1 and -2, and thrombospondin-4, whereas type IV collagen α3, type V collagen, fibrillin-1 and -2, thrombospondin-1, and endostatin were present in the corneal BM, but lacking or more weakly expressed in the limbal and conjunctival BMs. As compared to both the corneal and conjunctival BMs, the limbal BM showed a markedly increased immunoreactivity for laminin α1, α2, β1 chains, and agrin, and a specific but patchy immunoreactivity for laminin γ3 chain, BM40/SPARC, and tenascin-C, which co-localized with ABCG2/p63/K19-positive and K3/Cx43/desmoglein/integrin-α2-negative cell clusters comprising putative stem and early progenitor cells in the basal epithelium of the limbal palisades. Components that were particularly expressed in the corneal–limbal transition zone included type XVI collagen, fibulin-2, tenascin-C/R, vitronectin, bamacan, chondroitin sulfate, and versican, all of which co-localized with vimentin-positive cell clusters comprising putative late progenitor cells in the basal epithelium. This pronounced heterogeneity of the BM in the limbal area, both in the region of limbal palisades and the corneal–limbal transition zone, appears to be involved in providing unique microenvironments for corneal epithelial stem and late progenitor cells. Identification of specific niche parameters might not only help to understand limbal stem cell regulation, but also to improve their selective enrichment and in vitro expansion for therapeutic strategies.
The aim of the study was to quantify changes in donor and host corneal tissue after Descemet's stripping automated endothelial keratoplasty (DSAEK) using organ-cultured corneas and to correlate these ...findings with the visual acuity during intermediate-term follow-up.
Fifteen eyes of 15 consecutive patients, with Fuchs' endothelial dystrophy treated with DSAEK using organ-cultured corneas, underwent ophthalmological examination, including slit lamp-adapted optical coherence tomography, at 1, 3 and 7 days, and 4 weeks, 8 weeks and 6 months after the surgery.
The mean best spectacle-corrected visual acuity (BSCVA) improved from 20/100 pre-operatively to 20/40 at 6-months post-operatively (p<0.0001). A continuous decrease of thickness of the grafted lenticule was observed during the follow-up (mean thickness immediately after surgery 191(SD 56) mum, compared with 100 (SD 38) mum 6 months after surgery, p<0.001). The central corneal thickness decreased from 1057 (SD 86) mum at the first post-operative day to 661 (SD 74) mum after 6 months. Both central corneal thickness and the thickness of the posterior donor lamella correlated with the 6-month BSCVA (Pearson correlations -0.745 and -0.589, respectively, p<0.05).
Organ-cultured corneas can be used successfully for DSAEK. The thickness of the grafted corneal lenticule correlated with the BSCVA 6 months after the surgery. It decreased continuously during the follow-up period.
Airborne hyperspectral data have been available to researchers since the early 1980s and their use for geologic applications is well documented. The launch of the National Aeronautics and Space ...Administration Earth Observing 1 Hyperion sensor in November 2000 marked the establishment of a test bed for spaceborne hyperspectral capabilities. Hyperion covers the 0.4-2.5-/spl mu/m range with 242 spectral bands at approximately 10-nm spectral resolution and 30-m spatial resolution. Analytical Imaging and Geophysics LLC and the Commonwealth Scientific and Industrial Research Organisation have been involved in efforts to evaluate, validate, and demonstrate Hyperions's utility for geologic mapping in a variety of sites in the United States and around the world. Initial results over several sites with established ground truth and years of airborne hyperspectral data show that Hyperion data from the shortwave infrared spectrometer can be used to produce useful geologic (mineralogic) information. Minerals mapped include carbonates, chlorite, epidote, kaolinite, alunite, buddingtonite, muscovite, hydrothermal silica, and zeolite. Hyperion data collected under optimum conditions (summer season, bright targets, well-exposed geology) indicate that Hyperion data meet prelaunch specifications and allow subtle distinctions such as determining the difference between calcite and dolomite and mapping solid solution differences in micas caused by substitution in octahedral molecular sites. Comparison of airborne hyperspectral data from the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) to the Hyperion data establishes that Hyperion provides similar basic mineralogic information, with the principal limitation being limited mapping of fine spectral detail under less-than-optimum acquisition conditions (winter season, dark targets) based on lower signal-to-noise ratios. Case histories demonstrate the analysis methodologies and level of information available from the Hyperion data. They also show the viability of Hyperion as a means of extending hyperspectral mineral mapping to areas not accessible to aircraft sensors. The analysis results demonstrate that spaceborne hyperspectral sensors can produce useful mineralogic information, but also indicate that SNR improvements are required for future spaceborne sensors to allow the same level of mapping that is currently possible from airborne sensors such as AVIRIS.
The chemokine receptor CCR7 is essential for migration of mature dendritic cells (DCs) to the regional lymph nodes, and it has been shown that blocking of CCR7 improves graft survival after high-risk ...corneal transplantation in vascularized recipient corneas. However, it is so far unknown whether blocking of CCR7 reduces migration of DCs from the avascular cornea to the draining lymph nodes and whether this leads to improved graft survival also in the low-risk setting of corneal transplantation, which accounts for the majority of perforating transplantations performed. Therefore, in this study, pellets containing Freund's adjuvant and bovine serum albumin (BSA) conjugated to Alexa488 fluorescent dye were implanted into the corneal stroma of BALB/c mice to analyze antigen uptake by corneal DCs and their migration to the regional lymph nodes. After pellet implantation, mice were either treated by local administration of a CCR7 blocking fusion protein that consisted of CCL19 fused to the Fc part of human IgG1 or a control-IgG. In vivo fluorescence microscopy showed uptake of Alexa488-conjugated BSA by corneal DCs within 8 h. Furthermore, analysis of single cell suspensions of draining lymph nodes prepared after 48 h revealed that 2.1 ± 0.3% of CD11c+ cells were also Alexa488+. Importantly, DC migration was significantly reduced after topical administration of CCL19-IgG (1.2 ± 0.2%; p < 0.05). To test the effect of CCR7 blockade on graft rejection after allogeneic low-risk keratoplasty, corneal transplantations were performed using C57BL/6-mice as donors and BALB/c-mice as recipients. Treatment mice received two intraperitoneal loading doses of CCL19-IgG prior to transplantation, followed by local treatment with CCL19-IgG containing eye drops for the first two weeks after transplantation. Control mice received same amounts of control-IgG. Kaplan–Meier survival analysis showed that in the CCL19-IgG treated group, 76% of the grafts survived through the end of the 8 week observation period, whereas 38% of the grafts survived in the control group (p < 0.05). Taken together, our study shows that blockade of CCR7 reduces the migration of mature corneal DCs to the draining lymph nodes and leads to improved graft survival in low-risk corneal transplantation.
•Corneal dendritic cell (DC) migration is tracked using fluorescence-labeled pellets.•CCR7 blockade impairs DC migration from avascular corneas to draining lymph nodes.•CCR7 blockade promotes graft survival in low-risk murine corneal transplantation.
High-risk keratoplasties are usually performed after an uninflamed and quiescent interval in corneas with partly regressed blood and lymphatic vessels. We analysed whether the inhibition of ...post-keratoplasty revascularisation in mice with partly regressed corneal vessels ("intermediate-risk") improves graft survival.
Three interrupted stromal sutures (11-0) in corneas of Balb/c mice (6-8 weeks old) were placed for 6 weeks. Six months after suture removal, penetrating keratoplasty was performed with C57BL/6 donors. The treatment group received a vascular endothelial growth factor-A specific cytokine trap (VEGF Trap) intraperitoneally at days 0, 4, 7 and 14 after keratoplasty (25 mg/kg per mouse; controls received equal amounts of Fc protein). Pathological haemangiogenesis and lymphangiogenesis prior to as well as 3 days or 8 weeks after keratoplasty and graft survival were analysed.
Three days after keratoplasty corneal revascularisation was sufficiently reduced by VEGF Trap (haem-vascularised areas 42.7% reduction; lymph-vascularised areas 54.7% reduction). Survival proportions 8 weeks after keratoplasty were 36% in the treatment group compared with 9% in the control group (n = 11; p<0.05). At that time no differences in haemangiogenesis or lymphangiogenesis were observed between the two groups.
Early transient postoperative induction of haemangiogenesis and lymphangiogenesis and reformation of regressed corneal blood and lymphatic vessels are important for transplant rejections after "intermediate-risk" corneal transplantation.
The “Trauer Netzwerk Niedersachsen” („Bereavement Network Lower Saxony“ (BNLS)) aims at supporting families after the loss of a child or teenager due to various causes. This study aims to describe ...the experiences of bereaved family members with the BNLS counsellors. 12 semi-structured interviews were conducted with parents who had received or were currently receiving BNLS counselling. The interviews revealed the vital role counselling played aiding individuals cope with their grief. Participants valued the bereavement support, which was often lacking in their personal support networks. Counselling assisted parents in returning to daily life and caring for loved ones. Discussing “death” and “dying” helped participants find peace with their loss. Our findings suggest that bereavement counselling should be considered an essential component of healthcare for family members dealing with the loss of a child. Additionally, there is need for awareness and publicity for both the BNLS and its bereavement counselling services.
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