Epigenetics and cell death: DNA hypermethylation in programmed retinal cell death.

BackgroundVertebrate genomes undergo epigenetic reprogramming during development and disease. Emerging evidence suggests that DNA methylation plays a key role in cell fate determination in the retina. Despite extensive studies of the programmed cell death that occurs during retinal development and degeneration, little is known about how DNA methylation might regulate neuronal cell death in the retina.MethodsThe developing chicken retina and the rd1 and rhodopsin-GFP mouse models of retinal degeneration were used to investigate programmed cell death during retinal development and degeneration. Changes in DNA methylation were determined by immunohistochemistry using antibodies against 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC).ResultsPunctate patterns of hypermethylation paralleled patterns of caspase3-dependent apoptotic cell death previously reported to occur during development in the chicken retina. Degenerating rd1 mouse retinas, at time points corresponding to the peak of rod cell death, showed elevated signals for 5mC and 5hmC in photoreceptors throughout the retina, with the most intense staining observed in the peripheral retina. Hypermethylation of photoreceptors in rd1 mice was associated with TUNEL and PAR staining and appeared to be cCaspase3-independent. After peak rod degeneration, during the period of cone death, occasional hypermethylation was observed in the outer nuclear layer.ConclusionThe finding that cell-specific increases of 5mC and 5hmC immunostaining are associated with the death of retinal neurons during both development and degeneration suggests that changes in DNA methylation may play a role in modulating gene expression during the process of retinal degeneration. During retinal development, hypermethylation of retinal neurons associates with classical caspase-dependent apoptosis as well as caspase-3 independent cell death, while hypermethylation in the rd1 mouse photoreceptors is primarily associated with caspase-3 independent programmed cell death. These findings suggest a previously unrecognized role for epigenetic mechanisms in the onset and/or progression of programed cell death in the retina

Estimating individual cone fundamentals from their color-matching functions

Estimation of individual spectral cone fundamentals from color-matching functions is a classical and longstanding problem in color science. In this paper we propose a novel method to carry out this estimation based on a linear optimization technique, employing an assumption of a priori knowledge of the retinal absorptance functions. The result is an estimation of the combined lenticular and macular filtration for an individual, along with the nine coefficients in the linear combination that relates their color-matching functions to their estimated spectral-cone fundamentals. We test the method on the individual Stiles and Burch color-matching functions and derive cone-fundamental estimations for different viewing fields and matching experiment repetition. We obtain cone-fundamental estimations that are remarkably similar to those available in the literature. This suggests that the method yields results that are close to the true fundamentals

A case of atypical insertion of the levator scapulae

Anatomical variations in the musculature of the spine have the potential to cause functional and postural abnormalities, which in turn could lead to chronic myofascial and skeletal pain. We present a unilateral case of a 71-year-old Caucasian female in which the left levator scapulae muscle gave rise to an accessory head that inserted, by way of a flat aponeurotic band, to the ligamentum nuchae, the tendon of the rhomboideus major and the superior aspect of the serratus posterior superior muscle. The innervation was provided by a branch of the dorsal scapular nerve. By exerting unilateral traction on the vertebrae and surrounding musculature, this unusual variation might have resulted in clinical consequences including scoliosis and movement abnormalities of the head and neck as well as myofascial pain syndrome

‘Sons of athelings given to the earth’: Infant Mortality within Anglo-Saxon Mortuary Geography

FOR 20 OR MORE YEARS early Anglo-Saxon archaeologists have believed children are underrepresented in the cemetery evidence. They conclude that excavation misses small bones, that previous attitudes to reporting overlook the very young, or that infants and children were buried elsewhere. This is all well and good, but we must be careful of oversimplifying compound social and cultural responses to childhood and infant mortality. Previous approaches have offered methodological quandaries in the face of this under-representation. However, proportionally more infants were placed in large cemeteries and sometimes in specific zones. This trend is statistically significant and is therefore unlikely to result entirely from preservation or excavation problems. Early medieval cemeteries were part of regional mortuary geographies and provided places to stage events that promoted social cohesion across kinship systems extending over tribal territories. This paper argues that patterns in early Anglo-Saxon infant burial were the result of female mobility. Many women probably travelled locally to marry in a union which reinforced existing social networks. For an expectant mother, however, the safest place to give birth was with experience women in her maternal home. Infant identities were affected by personal and legal association with their mother’s parental kindred, so when an infant died in childbirth or months and years later, it was their mother’s identity which dictated burial location. As a result, cemeteries central to tribal identities became places to bury the sons and daughters of a regional tribal aristocracy

The outcome of trachomatous trichiasis surgery in Ethiopia: risk factors for recurrence.

BACKGROUND: Over 1.2 million people are blind from trachomatous trichiasis (TT). Lid rotation surgery is the mainstay of treatment, but recurrence rates can be high. We investigated the outcomes (recurrence rates and other complications) of posterior lamellar tarsal rotation (PLTR) surgery, one of the two most widely practised TT procedures in endemic settings. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a two-year follow-up study of 1300 participants who had PLTR surgery, conducted by one of five TT nurse surgeons. None had previously undergone TT surgery. All participants received a detailed trachoma eye examination at baseline and 6, 12, 18 and 24 months post-operatively. The study investigated the recurrence rates, other complications and factors associated with recurrence. Recurrence occurred in 207/635 (32.6%) and 108/641 (16.9%) of participants with pre-operative major (>5 trichiatic lashes) and minor (5 lashes (major recurrence). Recurrence was greatest in the first six months after surgery: 172 cases (55%) occurring in this period. Recurrence was associated with major TT pre-operatively (OR 2.39, 95% CI 1.83-3.11), pre-operative entropic lashes compared to misdirected/metaplastic lashes (OR 1.99, 95% CI 1.23-3.20), age over 40 years (OR 1.59, 95% CI 1.14-2.20) and specific surgeons (surgeon recurrence risk range: 18%-53%). Granuloma occurred in 69 (5.7%) and notching in 156 (13.0%). CONCLUSIONS/SIGNIFICANCE: Risk of recurrence is high despite high volume, highly trained surgeons. However, the vast majority are minor recurrences, which may not have significant corneal or visual consequences. Inter-surgeon variation in recurrence is concerning; surgical technique, training and immediate post-operative lid position require further investigation

A retrotracheal right subclavian artery in association with a vertebral artery and thyroidea ima

The retro-oesophageal right subclavian artery is an anatomical abnormality encountered by anatomists and pathologists and, more recently, interventional cardiologists and thoracic surgeons with an incidence of 0.2-2% in the population. We report a case of a retrotracheal right subclavian artery which originated distally along the left aortic arch and coursed between the trachea and the oesophagus. Additionally, the aortic arch gave rise to a common trunk, which subsequently bifurcated to yield to a right vertebral artery and a left thyroidea ima, replacing the left inferior thyroid artery. Consequently the right and the left recurrent laryngeal nerves were found to recur normally. The possible embryonic development of these branching patterns and their clinical significance is discussed

Degenerative changes in the appendicular joints of ancient human populations from the Japan Islands

Degenerative changes in six major limb joints were investigated to compare their prevalence among five ancient skeletal populations from the Japan Islands. The populations assessed in this study consisted of the farmers in the northern Kyushu/Yamaguchi area and the foragers from the northwestern Kyushu area from the Yayoi period (5th century BC to 3rd century AD); the Okhotsk (5th to 12th centuries AD) foragers from Hokkaido and Sakhalin; the common people from medieval Kamakura (12th to 14th centuries AD) in Kanto, central Japan; and the early-modern farmers (17th to 19th centuries AD) from Kumejima, in the southernmost island chain (Ryukyu Islands). Crude prevalence comparisons showed that the shoulder and hip joints were principally affected in early-modern Kumejima and medieval Kamakura, which contrasted with the high prevalence of elbow and knee joint changes in the Okhotsk people. The heavy dependence on marine mammals and fish for dietary protein intake probably required flexion and extension movements of the most severely degenerated joints in the Okhotsk people. The northern Kyushu/Yamaguchi and northwestern Kyushu Yayoi peoples were more affected by degeneration in the wrist joints than others, possibly due to their use of innovative tools such as stone or shell knives and harpoons. A multivariate logistic regression analysis, adjusted for age, region, and sex as the predictor variables for degenerative changes in joints, was applied to only the two samples from Kumejima and Kamakura (including previously reported spine data) because of their better preservation. This revealed differences in the prevalence of changes in some joints; for example, age-related changes were recognized. The Kumejima people were more commonly affected by hip and knee joint changes, whereas the Kamakura people were more commonly affected by changes to apophyseal joints. Because a stable isotope analysis indicated that the trophic levels of the two populations were almost the same, the pattern of degenerative changes would have reflected differences in their specific workloads, such as wet rice cultivation using a peculiar hoe by the Kumejima people. This study, combining multivariate logistic regression analysis of degenerative joint changes and stable isotope analyses, uses large skeletal populations to add clarity to the actual rigors of ancient life. © 2015 Elsevier Ltd and INQUA

Photobiomodulation devices for hair regrowth and wound healing: a therapy full of promise but a literature full of confusion.

yesPhotobiomodulation is reported to positively influence hair regrowth, wound healing, skin rejuvenation, and psoriasis. Despite rapid translation of this science to commercial therapeutic solutions, significant gaps in our understanding of the underlying processes remain. The aim of this review was to seek greater clarity and rationality specifically for the selection of optical parameters for studies on hair regrowth and wound healing. Our investigation of 90 reports published between 1985-2015 revealed major inconsistencies in optical parameters selected for clinical applications. Moreover, poorly understood photoreceptors expressed in skin such as cytochrome c oxidase, cryptochromes, opsins, may trigger different molecular mechanisms. All this could explain the plethora of reported physiological effects of light. To derive parameters for optimal clinical efficacy of photobiomodulation, we recommend a more rational approach, underpinning clinical studies with research of molecular targets and pathways using well-defined biological model systems enabling easy translation of optical parameters from in vitro to in vivo. Furthermore, special attention needs to be paid when conducting studies for hair regrowth, aiming for double-blind, placebo-controlled randomized clinical trials as the gold standard for quantifying hair growth.European Marie-Curie Actions Programme, Grant agreement no.: 60788

Definitions and standardization of a new grading scheme for eyelid contour abnormalities after trichiasis surgery

Background: Clear definitions of outcomes following trichiasis surgery are critical for planning program evaluations and for identifying ways to improve trichiasis surgery. Eyelid contour abnormality is an important adverse outcome of surgery; however, no standard method has been described to categorize eyelid contour abnormalities. Methodology/Principal Findings: A classification system for eyelid contour abnormalities following surgery for trachomatous trichiasis was developed. To determine whether the grading was reproducible using the classification system, six-week postoperative photographs were reviewed by two senior graders to characterize severity of contour abnormalities. Sample photographs defining each contour abnormality category were compiled and used to train four new graders. All six graders independently graded a Standardization Set of 75 eyelids, which included a roughly equal distribution across the severity scale, and weighted kappa scores were calculated. Two hundred forty six-week postoperative photographs from an ongoing clinical trial were randomly selected for evaluating agreement across graders. Two months after initial grading, one grader regraded a subset of the 240 photographs to measure longer-term intra-observer agreement. The weighted kappa for agreement between the two senior graders was 0.80 (95% CI: 0.71-0.89). Among the Standardization Set, agreement between the senior graders and the 4 new graders showed weighted kappa scores ranging from 0.60-0.80. Among 240 eyes comprising the clinical trial dataset, agreement ranged from weighted kappa 0.70-0.71. Longer-term intra-observer agreement was weighted kappa 0.86 (95% CI: 0.80-0.92). Conclusions/Significance: The standard eyelid contour grading system we developed reproducibly delineates differing levels of contour abnormality. This grading system could be useful both for helping to evaluate trichiasis surgery outcomes in clinical trials and for evaluating trichiasis surgery programs

Relationship between immediate post-operative appearance and 6-week operative outcome in trichiasis surgery

Background: Surgical technique, including suture placement and tension, is believed to contribute to the outcome of bilamellar tarsal rotation surgery for trachomatous trichiasis. However, the immediate post-operative appearance that minimizes the chance of recurrence and other adverse outcomes has not been investigated. Methodology/Principal Findings: To explore whether the degree of correction immediately after surgery is predictive of surgical outcome at the 6-week post-operative visit, photographs taken immediately after surgery were used to predict surgical outcomes, including the severity of eyelid contour abnormality and trichiasis recurrence. Both eyelid contour abnormalities and recurrence were accurately predicted from the immediate post-operative photographs by an experienced oculoplastic surgeon 85% and 70% of the time, respectively. Participants with a "slight over-correction" that resulted in no eyelid contour abnormality and no recurrence were used to identify immediate post-operative contours that lead to a successful surgical outcome. Conclusions/Significance: The immediate post-operative eyelid contour is an important indicator of post-operative success of BLTR surgery. Based upon our findings, we developed a Surgery Photocard. This card illustrates some examples of immediate post-surgical appearances, which led to a successful outcome, as well as sub-optimal appearances, which led to poor surgical outcomes. The card also provides suggestions for improving the appearance by adjusting the suture placement or tension based upon standard oculoplastic principles