Clinical Approach to Patients with Moderate-to-Severe Atopic Dermatitis: A Spanish Delphi Consensus.

Despite emerging evidence and advances in the management of atopic dermatitis there a lack of consensus regarding the diagnostic criteria, therapeutic approach, method to assess severity, and patient follow-up for this condition. An expert consensus study was conducted to provide recommendations on the management of patients with moderate-to-severe atopic dermatitis. The study used Delphi-like methodology based on a literature review, a summary of the scientific evidence, and a 2-round survey. The agreement of 60 panellists on 21 statements was evaluated. Consensus was pre-defined as ≥ 80% agreement of all respondents. In the first round 6 statements reached consensus. Unanimous consensus was achieved regarding therapeutic goals and patient satisfaction (maintained in the long term and periodic goals reassessment recommended every 3-6 months). In the second round, half of the statements reached consensus, all related to patient follow-up, treatment goals, and atopic comorbidities. The statements that did not reach consensus were related to diagnosis (biomarkers, allergy, and food testing) and starting patients on conventional systemic treatment rather than advanced treatment. The study assessed expert opinion regarding a variety of topics related to the clinical approach to patients with moderate-to-severe atopic dermatitis, in order to provide guidance on the diagnosis and management of patients with atopic dermatitis.

Inflammatory ER stress responses dictate the immunopathogenic progression of systemic candidiasis.

Recognition of pathogen-associated molecular patterns can trigger the inositol-requiring enzyme 1 α (IRE1α) arm of the endoplasmic reticulum (ER) stress response in innate immune cells. This process maintains ER homeostasis and also coordinates diverse immunomodulatory programs during bacterial and viral infections. However, the role of innate IRE1α signaling in response to fungal pathogens remains elusive. Here, we report that systemic infection with the human opportunistic fungal pathogen Candida albicans induced proinflammatory IRE1α hyperactivation in myeloid cells that led to fatal kidney immunopathology. Mechanistically, simultaneous activation of the TLR/IL-1R adaptor protein MyD88 and the C-type lectin receptor dectin-1 by C. albicans induced NADPH oxidase-driven generation of ROS, which caused ER stress and IRE1α-dependent overexpression of key inflammatory mediators such as IL-1ß, IL-6, chemokine (C-C motif) ligand 5 (CCL5), prostaglandin E2 (PGE2), and TNF-α. Selective ablation of IRE1α in leukocytes, or treatment with an IRE1α pharmacological inhibitor, mitigated kidney inflammation and prolonged the survival of mice with systemic C. albicans infection. Therefore, controlling IRE1α hyperactivation may be useful for impeding the immunopathogenic progression of disseminated candidiasis.

Effects of Cannabidiol, Hypothermia, and Their Combination in Newborn Rats with Hypoxic-Ischemic Encephalopathy.

Therapeutic hypothermia is well established as a standard treatment for infants with hypoxic-ischemic (HI) encephalopathy but it is only partially effective. The potential for combination treatments to augment hypothermic neuroprotection has major relevance. Our aim was to assess the effects of treating newborn rats following HI injury with cannabidiol (CBD) at 0.1 or 1 mg/kg, i.p., in normothermic (37.5°C) and hypothermic (32.0°C) conditions, from 7 d of age (neonatal phase) to 37 d of age (juvenile phase). Placebo or CBD was administered at 0.5, 24, and 48 h after HI injury. Two sensorimotor (rotarod and cylinder rearing) and two cognitive (novel object recognition and T-maze) tests were conducted 30 d after HI. The extent of brain damage was determined by magnetic resonance imaging, histologic evaluation, magnetic resonance spectroscopy, amplitude-integrated electroencephalography, and Western blotting. At 37 d, the HI insult produced impairments in all neurobehavioral scores (cognitive and sensorimotor tests), brain activity (electroencephalography), neuropathological score (temporoparietal cortexes and CA1 layer of hippocampus), lesion volume, magnetic resonance biomarkers of brain injury (metabolic dysfunction, excitotoxicity, neural damage, and mitochondrial impairment), oxidative stress, and inflammation (TNFα). We observed that CBD or hypothermia (to a lesser extent than CBD) alone improved cognitive and motor functions, as well as brain activity. When used together, CBD and hypothermia ameliorated brain excitotoxicity, oxidative stress, and inflammation, reduced brain infarct volume, lessened the extent of histologic damage, and demonstrated additivity in some parameters. Thus, coadministration of CBD and hypothermia could complement each other in their specific mechanisms to provide neuroprotection.

Colloidal Synthesis, Characterization, and Photoconductivity of Quasi-Layered CuCrS2 Nanosheets.

The current need to accelerate the adoption of photovoltaic (PV) systems has increased the need to explore new nanomaterials that can harvest and convert solar energy into electricity. Transition metal dichalcogenides (TMDCs) are good candidates because of their tunable physical and chemical properties. CuCrS2 has shown good electrical and thermoelectrical properties; however, its optical and photoconductivity properties remain unexplored. In this study, we synthesized CuCrS2 nanosheets with average dimensions of 43.6 ± 6.7 nm in length and 25.6 ± 4.1 nm in width using a heat-up synthesis approach and fabricated films by the spray-coating method to probe their photoresponse. This method yielded CuCrS2 nanosheets with an optical bandgap of ~1.21 eV. The fabricated film had an average thickness of ~570 nm, exhibiting a net current conversion efficiency of ~11.3%. These results demonstrate the potential use of CuCrS2 as an absorber layer in solar cells.

Invasiveness has no influence on the rate of incidental durotomies in surgery for multisegmental lumbar spinal canal stenosis (≥3 levels) with and without fusion: analysis from the German Spine Registry data (DWG-Register).

BACKGROUND: Nowadays, perioperative complications as dural tear (DT) with subsequent neurological deficits are documented in independent registers. However, the relationship of these complications with the grade of invasiveness (≥3 levels) is still unclear. The aim of this study was to evaluate perioperative complications, particularly DT with subsequent neurological deficits, between patients undergoing laminotomy and decompression and decompression and fusion in ≥3 levels. METHODS: Retrospective analysis of the data pool of the DWG register based on cases described by 10 clinics between January 2012 and December 2016 was performed. Surgically treated LSS in ≥3 segments were divided into decompression with or without instrumentation and fusion. Cases with intraoperative DT in both subgroups were analysed for risk factor occurrence. The Surgical Invasive Index (SII) was used. RESULTS: DT occurred in 102/941 (10.8%) patients. Difference in DT between groups was non-significant. The likelihood of DT increased by 2.12-fold with previous spinal surgery at the same level and by 1.9-fold for BMI 30-34 and >35 in comparison with BMI 26-29, respectively. Postoperative deep wound infection was increased by 2.39-fold after DT than without. Significance in outcomes between patients with/without DT was not found. The invasiveness index explained 48% of the variation in blood loss and 51% of the variation in surgery duration. CONCLUSIONS: The rate of incidental DT during decompression for LSS with and without fusion in ≥3 levels was associated with BMI and previous surgery at the same spinal level. Invasivness (SII) is valid rather for variables proper to surgery such as bledding and Op-time but no with incidence for DT and subsequent CSF-leackage.

Fabric Phase Sorptive Extraction of Selected Steroid Hormone Residues in Commercial Raw Milk Followed by Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

Hormones in edible matrices, such as milk, are a subject of concern because of their adverse effects on the endocrine system and cell signaling and the consequent disruption of homeostasis in human consumers. Therefore, the assessment of the presence of hormones in milk as potential endocrine-disrupting compounds is warranted. However, the complexity of milk as a sample matrix and the ultra-low concentration of hormones pose significant analytical challenges. Fabric phase sorptive extraction (FPSE) has emerged as a powerful analytical technique for the extraction of emerging pollutants from complex aqueous matrices. FPSE allows for substantially simplified sample handling and short extraction and desorption times, as well as the decreased use of organic solvents. It is considered a green alternative to traditional extraction methodologies. In this work, the FPSE technique was evaluated to perform the simultaneous extraction of 15 steroid hormones from raw milk without employing any sample pretreatment steps. Clean and preconcentrated hormone solutions obtained from FPSE of raw milk were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry to achieve low detection limits, which ranged from 0.047 to 1.242 ng·mL-1. Because of the presence of many interferents in milk, such as proteins, lipids, and sugar, the effect of fat content on the extraction procedure was also thoroughly studied. Additionally, for the first time, the effect of lactose on the extraction of steroid hormones was evaluated, and the results showed that the extraction efficiencies were enhanced in lactose-free samples. Finally, the optimized methodology was applied to commercial samples of cow and goat milk, and no measurable concentrations of the studied hormones were detected in these samples.

Analysis of Cranial Base Suture Fusion Patterns.

PURPOSE: It is known from both anatomic and radiographic studies that the majority of cranial sutures begin fusing in early adulthood and are fused by late adulthood. However, most of the studies focus on the cranial vault rather than the cranial base. Most clinicians treating patients with craniosynostosis are interpreting the behavior of cranial sutures on CT imaging. Therefore, the purpose of this study was to further clarify the radiographic appearance of cranial base sutures over the natural human life span. METHODS: Thirty CT scans of the head and face were reviewed for each decade starting at 1 year of life up to age 90. Scans were evaluated for the appearance of the occipitomastoid, petrosoocciptial, sphenosquamous, sphenopetrosal, frontosphenoidal, sphenozygomatic, petrososquamosal, frontoethmoidal, sphenoethmoidal and sphenoccipital sutures. Sutures were categorized as obliterated, present with fusion, present without fusion and unable to visualize. RESULTS: The majority of cranial base sutures are visible up through the eighth decade, although evidence of ossification across the suture starts as early as the second decade. Some sutures such as the occipitomastoid appeared > 90% open even as late as the ninth decade. Other sutures such as the sphenosquamosal and frontozygomatic are mostly fused by that age. CONCLUSION: Cranial base sutures appear to behave radiographically similar, to the cranial vault sutures in that they largely remain visible throughout adulthood but show varying amounts of ossification. There are some cranial base sutures which appear to remain open throughout life although the significance of this has yet to be determined.

Pharmaceutical and personal care product residues in a macrophyte pond-constructed wetland treating wastewater from a university campus: Presence, removal and ecological risk assessment.

Pharmaceuticals and personal care products (PPCPs) constitute a group of chemicals of concern because of their potential toxicity when reaching aquatic environments. Wastewaters are one of the main pathways of introduction into the environment of the chemical compounds used in PPCPs because, in most cases, wastewater treatment facilities are not 100% efficient in their removal. This problem is accentuated in rural zones and isolated communities where conventional treatment systems are too expensive to build and operate. Waste-stabilization ponds and constructed wetlands (CWs) are natural wastewater treatment systems which are used to improve the quality of sewage from small communities because of their low cost and easy maintenance. There is growing interest in combining the two technologies to make a more robust system, taking into account their respective strengths and weaknesses. In this work, a combined macrophyte pond-CW system was evaluated for the presence at three sampling points (influent, pond effluent and CW effluent) of fifteen steroid hormones and six benzotriazole ultraviolet stabilizers (BUVSs). None of the targeted BUVS compounds were detected in either the influent or effluent, probably because of the particular characteristics of the population served by the wastewater system. In contrast, eight different steroid hormone compounds were detected at concentrations ranging from 17.3 to 247.7 ng·L-1 in influent samples and from 8.1 to 22.1 ng·L-1 in final effluent samples. The pond-CW system showed high elimination rates of steroid hormone residues with average removal efficiencies of over 77%. This efficacy was confirmed in the ecological risk assessment evaluation that was performed. Final effluents showed a low ecological risk associated with steroid hormones in contrast to the medium-high ecological risks found in the influent samples.

Increased Calcium-Sensing Receptor Immunoreactivity in the Hippocampus of a Triple Transgenic Mouse Model of Alzheimer's Disease.

The Calcium-Sensing Receptor (CaSR) is a G-protein coupled, 7-transmembrane domain receptor ubiquitously expressed throughout the body, brain including. The role of CaSR in the CNS is not well understood; its expression is increasing during development, which has been implicated in memory formation and consolidation, and CaSR localization in nerve terminals has been related to synaptic plasticity and neurotransmission. There is an emerging evidence of CaSR involvement in neurodegenerative disorders and Alzheimer's disease (AD) in particular, where the over-production of ß-amyloid peptides was reported to activate CaSR. In the present study, we performed CaSR immunohistochemical and densitometry analysis in the triple transgenic mouse model of AD (3xTg-AD). We found an increase in the expression of CaSR in hippocampal CA1 area and in dentate gyrus in the 3xTg-AD mice when compared to non-transgenic control animals. This increase was significant at 9 months of age and further increased at 12 and 18 months of age. This increase paralleled the accumulation of ß-amyloid plaques with age. Increased expression of CaSR favors ß-amyloidogenic pathway following direct interactions between ß-amyloid and CaSR and hence may contribute to the pathological evolution of the AD. In the framework of this paradigm CaSR may represent a novel therapeutic target.

Role of parathyroid hormone in regeneration of irradiated bone in a murine model of mandibular distraction osteogenesis.

BACKGROUND: The purpose of this study was to measure the histologic and histomorphometric effects of parathyroid hormone (PTH) treatment on irradiated bone undergoing distraction osteogenesis (DO). METHODS: Thirty-four rats were divided into 3 groups. The control group underwent DO and the radiation control group underwent radiotherapy (RT) before DO. The PTH group underwent RT and received PTH during DO. Quantitative histology and histomorphometry were performed. RESULTS: RT resulted in a depletion of osteocytes and increase in empty lacunae. Treatment with PTH resulted in an increase in osteocyte counts and decrease in empty lacunae (p < .05), restoring osteocytes to levels seen in nonradiated bone (p = .121). RT decreased bone volume to tissue volume (BV-TV) ratio and increased osteoid volume to tissue volume (OV-TV) ratio, signifying increased immature bone formation. PTH treatment restored OV-TV ratio to that observed in nonradiated bone. CONCLUSION: PTH treatment of irradiated bone enhanced bone regeneration and restored osteocyte counts and OV-TV ratio to levels comparable to nonradiated bone. © 2016 Wiley Periodicals, Inc. Head Neck 39: 464-470, 2017.

Discrimination and Health among Lesbian, Gay, Bisexual and Trans People in Puerto Rico.

OBJECTIVE: To identify the experiences of discrimination among and the perceived priorities for the health of lesbian, gay, bisexual, and trans (LGBT) people in Puerto Rico (PR). METHODS: Data were collected during the 2013 LGBT Pride Parade in San Juan, using a brief self-administered survey that included questions on sociodemographic characteristics, the disclosure of sexual orientation/gender identity, experiences of discrimination, experiences while receiving social and health services, and perceived healthcare priorities and needs. RESULTS: Most participants reported that they had disclosed their sexual orientation to at least one person. Discrimination due to sexual orientation/gender identity was most frequently reported to have occurred in school settings. At least 25% of the sample reported regular or negative experiences based on sexual orientation/gender identity when receiving government services and when looking for support from relatives. HIV/AIDS, mental health, and sexual health were identified as healthcare priorities. In bivariate analyses, mental health services and aging were the priorities most frequently reported among older participants. HIV/AIDS was the main priority only for gay men; sexual health was the main priority for bisexuals; and mental health was the main priority for lesbians. Most participants reported that their preferred modalities for health service provision were support groups and health education. CONCLUSION: The experiences of discrimination among LGBT people in PR were consistent across age groups and sexual orientation/gender identity. Policies and interventions to address discrimination in different settings are necessary. The findings also suggest the need to prioritize HIV services among gay men and to address mental and sexual health needs among lesbian and bisexual people.

PATHOBIOLOGY OF NEURODEGENERATION: THE ROLE FOR ASTROGLIA.

The common denominator of neurodegenerative diseases, which mainly affect humans, is the progressive death of neural cells resulting in neurological and cognitive deficits. Astroglial cells are the central elements of the homoeostasis, defence and regeneration of the central nervous system, and their malfunction or reactivity contribute to the pathophysiology of neurodegenerative diseases. Pathological remodelling of astroglia in neurodegenerative context is multifaceted. Both astroglial atrophy with a loss of function and astroglial reactivity have been identified in virtually all the forms of neurodegenerative disorders. Astroglia may represent a novel target for therapeutic strategies aimed at preventing and possibly curing neurodegenerative diseases.

Bone marrow stem cells assuage radiation-induced damage in a murine model of distraction osteogenesis: A histomorphometric evaluation.

The purpose of this study is to determine if intraoperatively placed bone marrow stem cells (BMSCs) will permit successful osteocyte and mature bone regeneration in an isogenic murine model of distraction osteogenesis (DO) following radiation therapy (XRT). Lewis rats were split into three groups, DO only (Control), XRT followed by DO (xDO) and XRT followed by DO with intraoperatively placed BMSCs (xDO-BMSC). Coronal sections from the distraction site were obtained, stained and analyzed via statistical analysis with analysis of variance (ANOVA) and subsequent Tukey or Games-Howell post-hoc tests. Comparison of the xDO-BMSC and xDO groups demonstrated significantly improved osteocyte count (87.15 ± 10.19 vs. 67.88 ± 15.38, P = 0.00), and empty lacunae number (2.18 ± 0.79 vs 12.34 ± 6.61, P = 0.00). Quantitative analysis revealed a significant decrease in immature osteoid volume relative to total volume (P = 0.00) and improved the ratio of mature woven bone to immature osteoid (P = 0.02) in the xDO-BMSC compared with the xDO group. No significant differences were found between the Control and xDO-BMSC groups. In an isogenic murine model of DO, BMSC therapy assuaged XRT-induced cellular depletion, resulting in a significant improvement in histological and histomorphometric outcomes.

Complex and differential glial responses in Alzheimer's disease and ageing.

Glial cells and their association with neurones are fundamental for brain function. The emergence of complex neurone-glial networks assures rapid information transfer, creating a sophisticated circuitry where both types of neural cells work in concert, serving different activities. All glial cells, represented by astrocytes, oligodendrocytes, microglia and NG2-glia, are essential for brain homeostasis and defence. Thus, glia are key not only for normal central nervous system (CNS) function, but also to its dysfunction, being directly associated with all forms of neuropathological processes. Therefore, the progression and outcome of neurological and neurodegenerative diseases depend on glial reactions. In this review, we provide a concise account of recent data obtained from both human material and animal models demonstrating the pathological involvement of glia in neurodegenerative processes, including Alzheimer's disease (AD), as well as physiological ageing.

Prevention of radiation-induced bone pathology through combined pharmacologic cytoprotection and angiogenic stimulation.

Pathologic fractures and associated non-unions arising in previously irradiated bone are severely debilitating diseases. Although radiation is known to have deleterious effects on healthy tissue cellularity and vascularity, no clinically accepted pharmacologic interventions currently exist to target these destructive mechanisms within osseous tissues. We utilized amifostine-a cellular radioprotectant-and deferoxamine-an angiogenic stimulant-to simultaneously target the cellular and vascular niches within irradiated bone in a rat model of mandibular fracture repair following irradiation. Rats treated with combined therapy were compared to those undergoing treatment with singular amifostine or deferoxamine therapy, nontreated/irradiated animals (XFx) and non-treated/non-irradiated animals (Fx). 3D angiographic modeling, histology, Bone Mineral Density Distribution and mechanical metrics were utilized to assess therapeutic efficacy. We observed diminished metrics for all outcomes when comparing XFx to Fx alone, indicating the damaging effects of radiation. Across all outcomes, only the combined treatment group improved upon XFx levels, normalized all metrics to Fx levels, and was consistently as good as, or superior to the other treatment options (p<0.05). Collectively, our data demonstrate that pharmacologically targeting the cellular and vascular environments within irradiated bone prevents bone injury and enhances fracture healing.

Astroglia dynamics in ageing and Alzheimer's disease.

Ageing of the brain is the major risk factor for neurodegenerative disorders that result in cognitive decline and senile dementia. Ageing astrocytes undergo complex and region specific remodelling which can reflect life-long adaptive plasticity. In neurodegeneration, astroglial cells are similarly a subject for morpho-functional changes hampering the homoeostasis, defence and regeneration of the central nervous system. Region-specific astroglial atrophy with the loss of function and astroglial reactivity have been reported in virtually all forms of neurodegenerative pathologies. Modulating these astroglia changes may represent a fertile ground for novel therapeutic intervention strategies to prevent, delay progression and/or ameliorate pathology. While at present this bodacious goal represents a wishful thinking, further understanding of astroglial role in ageing and neurodegeneration could bring us closer to laying the foundations for such cell-specific therapeutic approaches.

Changes in Skin Vascularity in a Murine Model for Postmastectomy Radiation.

BACKGROUND: Postmastectomy radiation causes persistent injury to the breast microvasculature, and the prevailing assumption is that longer delays before breast reconstruction allow for recovery of blood supply. This study uses a murine model to examine the effects of radiation on skin vascularity to help determine when radiation-induced effects on the microvasculature begin to stabilize. STUDY DESIGN: Isogenic Lewis rats were divided into 2 groups: radiation therapy (XRT) (n = 24) and control (n = 24). The XRT rats received a breast cancer therapy human dose-equivalent of radiation to the groin, whereas control rats received no radiation. Animals were sacrificed at 4, 8, 12, and 16 weeks after completion of radiation. The vasculature was injected with Microfil, and groin skin was harvested for radiomorphometric analysis by microcomputed tomography. One-way analysis of variance with post hoc Tukey tests was used to determine significance between groups. RESULTS: Augmentation in vascularity was observed in the XRT group at 4 weeks after radiation compared to the control group (P = 0.045). Vessel number was decreased at 12 weeks (P = 0.002) and at 16 weeks (P = 0.001) in the XRT rats compared to control rats. Vessel separation in the XRT group was higher than that in the control group at 12 weeks (P = 0.009) and 16 weeks (P = 0.001). There was no change in vessel number and separation between weeks 12 and 16. CONCLUSIONS: A period of augmented skin vascularity is seen after radiation injury followed by decreased vascularity which demonstrates stabilization at approximately 12 weeks in this murine model. This model can be used to further study breast flap vascularity and the optimization of the timing of delayed breast reconstruction.

A Histomorphometric Analysis of Radiation Damage in an Isogenic Murine Model of Distraction Osteogenesis.

PURPOSE: The devastation radiation therapy (XRT) causes to endogenous tissue in patients with head and neck cancer can be a prohibitive obstacle in reconstruction of the mandible, demanding a better understanding of XRT-induced damage and options for reconstruction. This study investigated the cellular damage caused by radiation in an isogenic murine model of mandibular distraction osteogenesis (DO). The authors posited that radiation would result in fewer osteocytes, with increased empty lacunae and immature osteoid. MATERIALS AND METHODS: Twenty Lewis rats were randomly assigned to a DO group (n = 10) or a XRT/DO group (n = 10). These groups underwent an osteotomy and mandibular DO across a 5.1-mm gap. XRT was administered to the XRT/DO group at a fractionated human equivalent dose of 35 Gy before surgery. Animals were sacrificed on postoperative day 40 and mandibles were harvested and sectioned for histologic analysis. RESULTS: Bone that underwent radiation showed a significantly decreased osteocyte count and complementary increase in empty lacunae compared with non-XRT bone (P = .019 and P = .000). In addition, XRT bone exhibited increased immature osteoid and decreased mature woven bone compared with nonradiated bone (P = .001 and P = .003, respectively). Furthermore, analysis of the ratio of immature osteoid to woven bone volume exhibited a significant increase in the XRT bone, further showing the devastating damage from XRT (P = .001). CONCLUSION: These results clearly show the cellular diminution that occurs as a result of radiation. This foundational study provides the groundwork on which to investigate cellular therapies in an immuno-privileged model of mandibular DO.

Prophylactic administration of Amifostine protects vessel thickness in the setting of irradiated bone.

Although often beneficial in the treatment of head and neck cancer (HNC), radiation therapy (XRT) leads to the depletion of vascular supply and eventually decreased perfusion of the tissue. Specifically, previous studies have demonstrated the depletion of vessel volume fraction (VVF) and vessel thickness (VT) associated with XRT. Amifostine (AMF) provides protection from the detrimental effects of radiation damage, allowing for reliable post-irradiation fracture healing in the murine mandible. The purpose of this study is to investigate the prophylactic ability of AMF to protect the vascular network in an irradiated field. Sprague-Dawley rats (n = 17) were divided into 3 groups: control (C, n = 5), radiated (XRT, n = 7), and radiated mandibles treated with Amifostine (AMF XRT, n = 5). Both groups receiving radiation underwent a previously established, human equivalent dose of XRT totaling 35 Gy, equally fractionated over 5 days. The AMF XRT group received a weight dependent (0.5 mg AMF/5 g body weight) subcutaneous injection of AMF 45 min prior to XRT. Following a 56-day recovery period, mandibles were perfused, dissected, and imaged with µCT. ANOVA was used for comparisons between groups and p < 0.05 was considered statistically significant. Stereologic analysis demonstrated a significant and quantifiable restoration of VT in AMF treated mandibles as compared to those treated with radiation alone (0.061 ± 0.011 mm versus 0.042 ± 0.004 mm, p = 0.027). Interestingly, further analysis demonstrated no significant difference in VT between control mandibles and those treated with AMF (0.067 ± 0.016 mm versus 0.061 ± 0.011 mm, p = 0.633). AMF treatment also showed an increase in VVF, however those results were not statistically significant from VVF values demonstrated by the XRT group. Our data support the contention that AMF therapy acts prophylactically to protect vessel thickness. Based on these findings, we support the continued investigation of this treatment paradigm in its potential translation for the prevention of vascular depletion after radiotherapy.

Retinal macroglia changes in a triple transgenic mouse model of Alzheimer's disease.

The retinas of Alzheimer's disease (AD) patients and transgenic AD animal models display amyloid beta deposits and degeneration of ganglion cells. Little is known, however, about the glial changes in the AD retina. The present study used a triple transgenic mouse model (3xTG-AD), which carries mutated human amyloid precursor protein, tau, and presenilin 1 genes and closely mimics the human brain pathology, to investigate retinal glial changes in AD. AD cognitive symptoms are known to begin in the 3xTG-AD mice at four months of age but plaques and tangles are not seen until six to twelve months. Müller cells in 3xTG-AD animals were GFAP-positive, indicating activation, at the earliest time point investigated, nine months. Astrocyte activation was also suggested in the 3xTG-AD mice by an apparent increase in size and process number. Another glial marker, S100, was expressed by astrocytes in both the non-transgenic (NTG) controls and 3xTG-AD retinas. Labeling was predominantly nuclear in nine month non-transgenic (NTG) control mice but was also seen in the cytoplasm and processes at 18 months of age. Interestingly, the nuclear localization was not as prominent in the 3xTG-AD retina even at nine months with labeling observed in astrocyte processes. The diffusion of S100 suggests the possible secretion of this protein, as is seen in the brain, with age and, more profoundly, associated with AD. Several dense, abnormally shaped, opaque structures were noted in all 3xTG-AD mice investigated. These structures, which were enveloped by GFAP and S100-positive astrocytes and Müller cells, were positive for amyloid beta, suggesting that they are amyloid plaques. Staining control retinas with amyloid showed similar structures in 30% of NTG animals but these were fewer in number and not associated with glial activation. The results herein indicate retinal glia activation in the 3xTG-AD mouse retina.