Different Kinds Of Lesions Research Articles

CMNet: Cascaded context fusion and multi-attention network for multiple lesion segmentation of diabetic retinopathy images

Diabetic retinopathy (DR) is a leading cause of blindness in humans, and regular screening is helpful to early detection and containment of DR. Therefore, automated and accurate lesion segmentation is crucial for DR grading and diagnosis. However, it is full of challenges due to complex structures, inconsistent scales and blurry edges of different kinds of lesions. To address the above issues, this paper proposes a cascaded context fusion and multi-attention network (CMNet) for multiple lesion segmentation of DR images. The CMNet includes triple attention module (TAM), cascaded context fusion module (CFM) and balanced attention module (BAM). Firstly, TAM is proposed to extract channel attention, spatial attention and pixel-point attention features for addition fusion to ensure selectivity and consistency of information representation. Moreover, CFM applies adaptive average pooling and non-local operation to capture local and global contextual features for concatenation fusion to expand the receptive field of lesions. Finally, BAM computes foreground, background and boundary attention maps of lesions, as well as uses Squeeze-and-Excitation block to weigh the feature channels and rebalance attention of three regions to make the network focus on the edge details for fine segmentation. We performed comprehensive comparison experiments and ablation studies on three public datasets of DDR, IDRiD and E-Ophtha, and mAUC of four lesions segmentation reached 0.6765, 0.7466 and 0.6710, respectively. The experimental results show that the proposed model outperforms current state-of-the-arts, which overcomes the adverse interference of background noise, and preserves contour details for realizing precise segmentation of multi-scale lesion.

Three-Year Perspective Study on American Kestrels (Falco sparverius) Received for Rehabilitation in a Facility in Southern Brazil

The American kestrel is a common bird of prey across Brazil and is abundant in many regions of the country. Kestrels are also found in urban areas, which predispose them to anthropogenic threats. Some threats that wild raptors face around the world include electrocution, barbed-wire lesions, shooting, collision with artificial structures, and vehicle-related accidents. Raptors are often brought to veterinary clinics with traumatic lesions arising from such threats. Infectious diseases are also a primary reason for raptors to be brought to veterinary facilities as well as nestlings and young those are found outside the nest or young. The aim of our study was to report the frequency and causes of injuries in American kestrels (F. sparverius) received at a rehabilitation facility in southern Brazil. We evaluated data collected from 2019 to 2021 for a total of 82 individuals, including 47 adults and 35 juveniles, which composed 57.3% and 35% of our dataset, respectively. We found that physical trauma was the main reason for admission (61% or 50/82 of all cases we examined). Traumatic injuries included bone fractures, traumatic brain injury, lacerations, and different kinds of lesions. Juveniles with no signs of trauma or diseases represented the second main cause of admission to the rehabilitation facility (28% or 23/82 individuals). Most individuals were admitted to the rehabilitation clinic in December (37.8%), followed by November (20.7%) and January (4.6%). We found that the outcomes of rehabilitation were generally positive. Of the 82 individuals received, 44 (53%) were released back to the wild, 20 (24%) were euthanized for humane reasons and 19 (23%) died as a result of their injuries or illness. Future work on the frequency of anthropogenically-induced injuries and illnesses will help shed more light on rehabilitation strategies that lead to successful outcomes for raptor species.

EAD-Net: A Novel Lesion Segmentation Method in Diabetic Retinopathy Using Neural Networks.

Diabetic retinopathy (DR) is a common chronic fundus disease, which has four different kinds of microvessel structure and microvascular lesions: microaneurysms (MAs), hemorrhages (HEs), hard exudates, and soft exudates. Accurate detection and counting of them are a basic but important work. The manual annotation of these lesions is a labor-intensive task in clinical analysis. To solve the problem, we proposed a novel segmentation method for different lesions in DR. Our method is based on a convolutional neural network and can be divided into encoder module, attention module, and decoder module, so we refer it as EAD-Net. After normalization and augmentation, the fundus images were sent to the EAD-Net for automated feature extraction and pixel-wise label prediction. Given the evaluation metrics based on the matching degree between detected candidates and ground truth lesions, our method achieved sensitivity of 92.77%, specificity of 99.98%, and accuracy of 99.97% on the e_ophtha_EX dataset and comparable AUPR (Area under Precision-Recall curve) scores on IDRiD dataset. Moreover, the results on the local dataset also show that our EAD-Net has better performance than original U-net in most metrics, especially in the sensitivity and F1-score, with nearly ten percent improvement. The proposed EAD-Net is a novel method based on clinical DR diagnosis. It has satisfactory results on the segmentation of four different kinds of lesions. These effective segmentations have important clinical significance in the monitoring and diagnosis of DR.

Assessment of the Characteristics of Different Kinds of MS Lesions Using Multi-Parametric MRI

Background: Studying different pathological aspects of lesions in multiple sclerosis (MS) patients could be useful to modify the diagnosis and treatment of this neurological disorder. Magnetic resonance imaging (MRI) modalities have the potential to investigate variations in brain tissue because of inflammatory and neurodegenerative processes in various types of MS-related lesions. Objectives: This study was done to investigate the quantitative changes in MRI-based parameters, like perfusion and magnetization transfer ratio (MTR) of different types of brain lesions, to demonstrate the ability of MRI to detect structural and pathological differences in MS lesions. Methods: Quantitative MRI modalities were performed on 18 patients with five different kinds of lesions (T1 holes, acute and chronic white matter (WM), and acute and chronic gray matter (GM) lesions) using a 3 T MRI scanner. The following protocols were used to characterize the pathology of lesions: (I) fluid-attenuated inversion recovery (FLAIR); (II) pre- and post-contrast T1-weighted; (III) dynamic contrast-enhanced (DCE); and (IV) MTR imaging. Quantitative comparison of Ktrans, cerebral blood volume (CBV), cerebral blood flow (CBF), and MTR was done to find the best parameter to distinguish different lesions. Finally, a multivariate classifier was applied to introduce the best parameter to indicate differences in lesions. Results: Five lesions were characterized by perfusion and MTR parameters. The pathological changes were measured, including: (I) the highest value of parameters in both acute WM and GM lesions; (II) the lowest value of four parameters in both chronic WM and GM lesions; (III) MTR had the highest rank among parameters using the classifier. Conclusions: The degree of pathological alterations due to inflammatory and neurodegenerative processes in MS-related lesions was indicated through the used parameters in different kinds of lesions. Inflammation was the dominant process in acute lesions, while neurodegeneration and tissue loss were observed mostly in chronic lesions. Both inflammation and neurodegeneration were detected in T1 holes. Perfusion parameters and MTR were reasonable parameters to describe differences in brain lesions. Thus, it could be confirmed that magnetization transfer imaging (MTI) and DCE-MRI are high-sensitivity methods to detect microstructural changes in the brain and subtle changes in the blood-brain-barrier. Classification of the parameters indicated that MTR was the best biomarker than others to show variations in lesions pathology.

Trauma abdominal contuso por golpe con manubrio de bicicleta

Introducción: Los accidentes en bicicleta son una causa frecuente de trauma abdominal contuso en pediatría. En Chile no existen publicaciones científicas que traten sobre las lesiones abdominales por manubrio de bicicleta, su presentación y manejo.Objetivo: Describir tres casos clínicos de trauma abdominal contuso provocados por manubrio de bicicleta en niños, ilustrar las distintas lesiones observadas, sus formas de presentación y manejo.Casos Clínicos: 1) Paciente masculino, 11 años, consulta tras golpe con manubrio de bicicleta en epigastrio; en la Tomografía Computada (TC) de abdomen y pelvis se describió neumoretroperitoneo. Se realizó laparotomía exploradora, reparándose una perforación duodenal. 2) Paciente masculino, 14 años, consulta tras golpe en el hipocondrio izquierdo con el manubrio de la bicicleta; en la TC se evidenció fractura esplénica con múltiples laceraciones. Por la presencia de sangrado activo se trató con angioembolización, lográndose resolución de la lesión y viabilidad del órgano luego de 6 semanas de seguimiento. 3) Paciente masculino, 9 años, ingresó tras sufrir golpe con manubrio de bicicleta en el hipocondrio derecho. En TC se observó una laceración hepática, que fue manejada de forma expectante, con resolución de la lesión luego de 8 semanas de seguimiento. Todos los pacientes tuvieron una evolución favorable.Conclusión: El trauma abdominal contuso por golpe con manubrio de bicicleta puede ser potencialmente grave en pacientes pediátricos, pudiendo afectar órganos sólidos y vísceras huecas. El manejo no quirúrgico cada vez es más utilizado, logrando altas tasas de éxito en pacientes estables. Los pacientes inestables o en los que se sospeche perforación de víscera hueca, requerirán cirugía como primera aproximación.

MRI findings of obstructive azoospermia: lesions in and out of pelvic cavity.

Obstructive azoospermia (OA) is caused by excurrent duct obstruction, which can occur anywhere along the course of the male reproductive tract and is classically characterized by normal spermatogenesis. To be familiar with the imaging anatomy of normal and abnormal male genital ducts is essential to the diagnosis of OA. In some circumstances, OA can also be related to some specific syndromes; thus, making an accurate diagnosis may require an integral view of the whole abdomen and pelvis. MR is a great complementary imaging modality either for the detection of obstructive factors, especially for characterization of those indeterminate features on ultrasound, or for the identification of specific syndromes related to OA. In this article, a series of patients with OA caused by different kinds of lesions in and out of the pelvic cavity (abdomen) shown on MR imaging were included, and some cases of specific syndromes related to OA were also reviewed.

Endoscopic and Microsurgical Approaches to the Cavernous Sinus – Anatomical Review

AbstractCavernous sinus surgery has always represented a surgical challenge due to the great importance of the surrounding anatomical structures and to the high morbidity associated to it. Although the anatomy of this region has been extensively described, controversy remains related to the best treatment and approaches for different kinds of lesions. In this article, a literature review was performed on the surgical anatomy and approaches to the cavernous sinus.

Histopathology Findings of Asphyxia in Lungs of Hanging and Drowning Deaths

Sometimes mysterious circumstances accompanied by inadequate external and internal findings related to ligature mark in hanging deaths as well as scarcity of classical lung features in drowning deaths makes it difficult to conclude or rule out cause of death as asphyxia. To form opinion regarding cause of death as hanging and drowning in such cases, documenting histopathology findings of lungs as supplementary autopsy evidence based on the theory that asphyxia comprises different kinds of lesions that can produce varied histopathology findings is really a meaningful exercise. Hanging and drowning being the most common prevalent asphyxia types in India, 47 hanging and 28 drowning deaths were studied to find more common histopathology findings for each group of asphyxia. Cause of deaths of the cases confirmed after meticulous post mortem examinations and police investigations. Histopathology section from lungs of every case was prepared and stained with Haematoxylin-Eosin. As compared to drowning, the histopathology findings of alveolar tissue collapse, alveolar overinsufflation, bronchiolar constriction and bronchiolar dilatations, congestion, interstitial edema and alveolar hemorrhage were more commonly observed in lungs of hanging. The only histopathology finding that was more commonly noticed in lungs of drowning was intra-alveolar edema.

Alternative solutions and new scenarios for translesion DNA synthesis by human PrimPol.

PrimPol is a recently described DNA polymerase that has the virtue of initiating DNA synthesis. In addition of being a sensu stricto DNA primase, PrimPol's polymerase activity has a large capacity to tolerate different kind of lesions. The different strategies used by PrimPol for DNA damage tolerance are based on its capacity to "read" certain lesions, to skip unreadable lesions, and as an ultimate solution, to restart DNA synthesis beyond the lesion thus acting as a TLS primase. This lesion bypass potential, revised in this article, is strengthened by the preferential use of moderate concentrations of manganese ions as the preferred metal activator. We show here that PrimPol is able to extend RNA primers with ribonucleotides, even when bypassing 8oxoG lesions, suggesting a potential new scenario for PrimPol as a TLS polymerase assisting transcription. We also show that PrimPol displays a high degree of versatility to accept or induce distortions of both primer and template strands, creating alternative alignments based on microhomology that would serve to skip unreadable lesions and to connect separate strands. In good agreement, PrimPol is highly prone to generate indels at short nucleotide repeats. Finally, an evolutionary view of the relationship between translesion synthesis and primase functions is briefly discussed.

Signs and Symptoms inComadia redtenbacheriHamm. (Lepidoptera: Cossidae) Larvae Affected by Parasitoids

Abstract. Comadia redtenbacheri Hamm. larvae are collected for human consumption in Mexico. The larvae often show different kinds of lesions, caused by ichneumonid or tachinid endoparasitoids, friction, or fungi. Lesions on agave red worm larvae caused by the parasitoids Acantholespesia texana (Aldrich & Webber) and Lissonota fascipennis Townes appear as an internal melanized structure, although the form and position vary depending on the parasitoid. It is possible to select healthy larvae by observing different kinds of lesions.

Kinetic and perfusion modeling of hyperpolarized (13)C pyruvate and urea in cancer with arbitrary RF flip angles.

The accurate detection and characterization of cancerous tissue is still a major problem for the clinical management of individual cancer patients and for monitoring their response to therapy. MRI with hyperpolarized agents is a promising technique for cancer characterization because it can non-invasively provide a local assessment of the tissue metabolic profile. In this work, we measured the kinetics of hyperpolarized [1-(13)C] pyruvate and (13)C-urea in prostate and liver tumor models using a compressed sensing dynamic MRSI method. A kinetic model fitting method was developed that incorporated arbitrary RF flip angle excitation and measured a pyruvate to lactate conversion rate, Kpl, of 0.050 and 0.052 (1/s) in prostate and liver tumors, respectively, which was significantly higher than Kpl in healthy tissues [Kpl =0.028 (1/s), P<0.001]. Kpl was highly correlated to the total lactate to total pyruvate signal ratio (correlation coefficient =0.95). We additionally characterized the total pyruvate and urea perfusion, as in cancerous tissue there is both existing vasculature and neovascularization as different kinds of lesions surpass the normal blood supply, including small circulation disturbance in some of the abnormal vessels. A significantly higher perfusion of pyruvate (accounting for conversion to lactate and alanine) relative to urea perfusion was seen in cancerous tissues (liver cancer and prostate cancer) compared to healthy tissues (P<0.001), presumably due to high pyruvate uptake in tumors.

Basic technique in endoscopic ultrasound-guided fine needle aspiration for solid lesions: How many passes?

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has evolved to become an indispensable tool for tissue acquisition in patients with luminal and extra luminal gastrointestinal cancers. Despite the extensive use of EUS-FNA, there still exists a wide variation in the number of samples required to ensure acquisition of diagnostic material from different kind of lesions. There are several factors that may influence the number of fine needle passes made during EUS-FNA, but the main factor seems to be the presence of a Cytopathologist during the EUS procedure. The diagnostic yield of EUS-FNA with rapid on-site evaluation (ROSE) in most studies exceeds 90%. Nevertheless, ROSE is not available in many centers. Various studies have investigated the adequate number of needle passes that should be performed if ROSE is not used. Differences exist based on the nature of the target lesion: Five to seven passes for pancreatic masses, three passes for lymphnodes, only one pass for pancreatic cystic lesions. Consider using a core biopsy needle or a 19-G FNA needle for histology could improve the diagnostic yield. Even though EUS-FNA is widely available, some patients still do not receive conclusive diagnoses upon initial EUS-FNA. One way to maximize the benefits for patients might be to centralize cases to several well-equipped, high-volume centers with experienced endosonographers that have universal availability of ROSE.

Adaptive response in human blood lymphocytes exposed to non-ionizing radiofrequency fields: resistance to ionizing radiation-induced damage.

The aim of this preliminary investigation was to assess whether human peripheral blood lymphocytes which have been pre-exposed to non-ionizing radiofrequency fields exhibit an adaptive response (AR) by resisting the induction of genetic damage from subsequent exposure to ionizing radiation. Peripheral blood lymphocytes from four healthy donors were stimulated with phytohemagglutinin for 24 h and then exposed for 20 h to 1950 MHz radiofrequency fields (RF, adaptive dose, AD) at an average specific absorption rate of 0.3 W/kg. At 48 h, the cells were subjected to a challenge dose (CD) of 1.0 or 1.5 Gy X-irradiation (XR, challenge dose, CD). After a 72 h total culture period, cells were collected to examine the incidence of micronuclei (MN). There was a significant decrease in the number of MN in lymphocytes exposed to RF + XR (AD + CD) as compared with those subjected to XR alone (CD). These observations thus suggested a RF-induced AR and induction of resistance to subsequent damage from XR. There was variability between the donors in RF-induced AR. The data reported in our earlier investigations also indicated a similar induction of AR in human blood lymphocytes that had been pre-exposed to RF (AD) and subsequently treated with a chemical mutagen, mitomycin C (CD). Since XR and mitomycin-C induce different kinds of lesions in cellular DNA, further studies are required to understand the mechanism(s) involved in the RF-induced adaptive response.

Original article Transcription factor Pax6 is expressed by astroglia after transient brain ischemia in the rat model

Reactive astrogliosis is regarded as an universal astrocytic response to different kinds of lesions, concerned with glial fibrillary acidic protein (GFAP) up-regulation, cellular hypertrophy and proliferation. The origin of reactive and proliferating cells in the adult brain is still disputable. Persistent progenitors as well as de-differentiating adult cells of various glial lineages are regarded as possible candidates. Pax6 transcription factor is one of the characteristic markers of astroglial de-differentiation, also important for regulation of neural and glial proliferation. Various kinds of pathological stimuli evoke reactive response, differentiated in its morphological, biochemical and immunological character. The aim of this study was to assess the dynamics of astroglial morphological and proliferative response to ischemic injury. One-hour transient focal cerebral ischemia was applied to evoke the reactive astrogliosis in twenty five adult male Wistar rats. The astrocytic morphological and proliferative reactions to ischemia were studied in the period of 6 weeks by means of GFAP and Pax6 immunofluorescent staining. A strong reactive astroglial response was observed in the cerebral cortex and striatum, manifested by GFAP and Pax6 up-regulation and astrocytic hypertrophy. Apparent morphological changes appeared within 24 hrs after ischemia. The GFAP/Pax6 colocalization was numerous and observed 24 hrs after ischemia. A characteristic spatial distribution of GFAP/Pax6 double-labelled astrocytes and Pax6 single-labelled nuclei was revealed, with the latter situated more distantly from the ischemic core. The maximal intensity of astrocytic reaction was present from the first post-ischemic week. Astroglial hypertrophic changes and proliferative reaction were more intense in the striatum than in the cerebral cortex. Our observations reveal intensive astroglial de-differentiation and proliferative response, reflected by dynamic Pax6 up-regulation within GFAP-immunoreactive astrocytes. Transient cerebral ischemia evokes strong reactive astrogliosis, which is apparently differentiated in respect to the post-ischemic period and particular brain structure.

New Insights into the Link Between DNA Damage and Apoptosis

When lesions are unrepaired or there are defects in the DNA repair system, DNA damage is often correlated to apoptosis. However, different kinds of lesions and different degrees of lesion severity can trigger numerous signaling responses. DNA repair proteins involved in specific DNA repair pathways can modulate the function or activity of some apoptotic factors, further emphasizing the crosstalk between DNA damage and cell death. Here, we discuss the signaling networks that link DNA damage to apoptosis, and we focus on post-translational modifications, leading to crucial changes in protein behavior, following various kinds of DNA damage. Moreover, we analyze the existence of apoptosis-related functions of typical repair proteins, leading to diverse, often-overlapping, DNA damage responses. The better understanding of the regulation and the functionality of key DNA repair proteins, also involved in apoptosis regulation, has the potential of modulating the cell outcomes on DNA damage, particularly in the context of cancer treatment.

Deciphering the elusive nature of sharp bone trauma using epifluorescence macroscopy: a comparison study multiplexing classical imaging approaches

Characterization of sharp-force trauma on human bones can be extremely useful in providing information regarding the nature and context of death. Nevertheless, in the identification of weapons used to cause sharp-force trauma and analysis of bone wounds, challenging tasks still remain. Current analysis attempting to dissect bone wound characteristics varied quite a lot and mixed different criteria, thus leading sometimes to conflicting results. In this context, the aim of our study is to clarify qualitative aspects of cut marks induced by sharp weapons on human bones. For that purpose, we analyzed bone samples via an original approach based on bone autofluorescence with an epifluorescence macroscope and compared it to previous existing methods. In this study, we used bone sections from human clavicles on which three different kinds of lesions were manually implemented, using different weapons. The bone wounds were analyzed by three different methodologies, light microscopy, scanning electron microscopy (SEM), and micro-computed tomography, and were compared with epifluorescence macroscopy. We paid attention more significantly to the aspect of walls and floor of the kerf, so as to conclude on the nature and distinguish between weapons used. Among all technologies used in this study, the most precise and efficient methods were epifluorescence macroscopy and SEM. Nonetheless, epifluorescence macroscopy is faster, cheaper, and more accessible than SEM. More significantly, this technique, which has the potential to accurately document the nature of the damage, is nondestructive, and could thus be highly useful in forensic science as anthropology.

Role and interaction of p53, BAX and the stress-activated protein kinases p38 and JNK in benzo(a)pyrene-diolepoxide induced apoptosis in human colon carcinoma cells

Polycyclic aromatic hydrocarbons are ubiquitous environmental pollutants formed during incomplete combustion of organic material. For example benzo[a]pyrene (B[a]P) is a constituent and contaminant of cigarette smoke, automobile exhaust, industrial waste and even food products. B[a]P is carcinogenic to rodents and humans. B[a]P induces its own metabolism, which generates different metabolites such as the highly reactive electrophilic genotoxin and ultimal carcinogen B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE). BPDE can bind to nucleophilic macromolecules such as proteins and DNA and causes mutations. Multiple defence mechanisms have evolved to protect the cell from DNA damage. Specific signalling pathways operate to detect and repair different kinds of lesions. In case, the damage is poorly removed expansion of damaged cells can be counteracted, e.g., by the inhibition of proliferation or triggering apoptosis. Examples of damage sensors and transducers are stress-activated protein kinases (SAPKs) and the tumour suppressor protein p53. Here, we studied the role of p53 and the pro-apoptotic protein BAX in BPDE-induced cell death by using wild-type- or knock-out-human colon carcinoma cells. As reported previously, we could reconfirm a critical role of p53 in BPDE-induced apoptosis. Furthermore, induced levels of total p53 and its transcriptional target p21 declined at higher BPDE concentrations correlating with reduced rates of apoptosis. Interestingly, increased phosphorylation of p53 at serine 15 remained elevated at higher BPDE concentrations thus disconnecting p53 phosphorylation from downstream apoptosis. Hence, phosphorylation of p53 seems not only to be a more sensitive biomarker of BPDE exposure but might serve other functions unrelated to apoptosis. In addition, we identify BAX as a novel and essential factor to trigger the intrinsic pathway of apoptosis in response to BPDE. Furthermore, BPDE in parallel activates the SAPKs p38 and JNK, which are as well involved in apoptosis. Although several routes of mutual regulation of p53 and SAPK have been described, we present evidence that the SAPK pathway in response to genotoxic stress can unexpectedly operate independently of p53 and controls apoptosis by a novel mechanism possibly downstream of caspases.

An osseous lesion in a 10-year-old boy with Hodgkin's lymphoma: a case report

IntroductionOsseous involvement of Hodgkin's lymphoma is uncommon. When osteolytic lesions are seen on imaging it is important to evaluate potential other causes.Case presentationWe report the case of a 10-year-old Caucasian boy who presented to our facility with a bony lesion of the right clavicle and enlarged cervical lymph nodes. A simultaneous biopsy of the lymph node and of the osteolytic process of his right proximal clavicle was performed and revealed two different kinds of lesions: a mixed cellularity Hodgkin's lymphoma and an osteochondroma.ConclusionsSince the latter is a common benign bone tumor, which should not interfere with the staging of the lymphoma, we emphasize the importance of ensuring that all efforts are made to acquire a diagnostic biopsy of all atypical lesions.

Integrated Analysis of Vascular and Nonvascular Changes From Color Retinal Fundus Image Sequences

Algorithms are presented for integrated analysis of both vascular and nonvascular changes observed in longitudinal time-series of color retinal fundus images, extending our prior work. A Bayesian model selection algorithm that combines color change information, and image understanding systems outputs in a novel manner is used to analyze vascular changes such as increase/decrease in width, and disappearance/appearance of vessels, as well as nonvascular changes such as appearance/disappearance of different kinds of lesions. The overall system is robust to false changes due to inter-image and intra-image nonuniform illumination, imaging artifacts such as dust particles in the optical path, alignment errors and outliers in the training-data. An expert observer validated the algorithms on 54 regions selected from 34 image pairs. The regions were selected such that they represented diverse types of vascular changes of interest, as well as no-change regions. The algorithm achieved a sensitivity of 82% and a 9% false positive rate for vascular changes. For the nonvascular changes, 97% sensitivity and a 10% false positive rate are achieved. The combined system is intended for diverse applications including computer-assisted retinal screening, image-reading centers, quantitative monitoring of disease onset and progression, assessment of treatment efficacy, and scoring clinical trials.

New functions of XPC in the protection of human skin cells from oxidative damage.

Xeroderma pigmentosum (XP) C is involved in the recognition of a variety of bulky DNA-distorting lesions in nucleotide excision repair. Here, we show that XPC plays an unexpected and multifaceted role in cell protection from oxidative DNA damage. XP-C primary keratinocytes and fibroblasts are hypersensitive to the killing effects of DNA-oxidizing agents and this effect is reverted by expression of wild-type XPC. Upon oxidant exposure, XP-C primary keratinocytes and fibroblasts accumulate 8,5'-cyclopurine 2'-deoxynucleosides in their DNA, indicating that XPC is involved in their removal. In the absence of XPC, a decrease in the repair rate of 8-hydroxyguanine (8-OH-Gua) is also observed. We demonstrate that XPC-HR23B complex acts as cofactor in base excision repair of 8-OH-Gua, by stimulating the activity of its specific DNA glycosylase OGG1. In vitro experiments suggest that the mechanism involved is a combination of increased loading and turnover of OGG1 by XPC-HR23B complex. The accumulation of endogenous oxidative DNA damage might contribute to increased skin cancer risk and account for internal cancers reported for XP-C patients.