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Neuroinflammation is causally associated with Alzheimer's disease (AD) pathology. Reactive glia cells secrete various neurotoxic factors that impair neuronal homeostasis eventually leading to neuronal loss. Although the glial activation mechanism in AD has been relatively well studied, how it perturbs intraneuronal signaling, which ultimately leads to neuronal cell death, remains poorly understood. Here, we report that compound stimulation with the neurotoxic factors TNF and glutamate aberrantly activates neuronal TAK1 (also known as MAP3K7), which promotes the pathogenesis of AD in mouse models. Glutamate-induced Ca2+ influx shifts TNF signaling to hyper-activate TAK1 enzymatic activity through Ca2+/calmodulin-dependent protein kinase II, which leads to necroptotic cellular damage. Genetic ablation and pharmacological inhibition of TAK1 ameliorated AD-associated neuronal loss and cognitive impairment in the AD model mice. Our findings provide a molecular mechanism linking cytokines, Ca2+ signaling and neuronal necroptosis in AD.

To evaluate the change in intraocular pressure (IOP) in patients with idiopathic intracranial hypertension (IIH) who underwent optic nerve sheath fenestration (ONSF) and to determine if radiographic evidence of posterior scleral or globe indentation influenced IOP.This is a retrospective analysis of IOP in IIH patients who underwent ONSF. The study included all patients from September 2010 to March 2018 operated on by a single surgeon (R.M.). IOPs preoperatively and postoperatively were recorded along with the acetazolamide dosage and whether there was evidence of posterior scleral or globe indentation on preoperative MRI.A total of 29 patients (35 eyes) with IIH underwent ONSF. The average reduction in IOP among all patients was 1.24 mm Hg (P = 0.0218), but this increased to 2.69 mm Hg (P = 0.004) in patients who were maintained on the same dosage of acetazolamide in the preoperative and postoperative period. Furthermore, the reduction in IOP in those with posterior scleral or globe indentation was 2.5 mm Hg (P = 0.0095). When the perioperative period was evaluated, the mean decrease in IOP was 1.83 mm Hg (P = 0.0217).Reducing the cerebral spinal fluid pressure (CSFP) at the level of the intraorbital optic nerve through an ONSF can slightly reduce the IOP. In those with evidence of posterior globe or scleral indentation/flattening, the reduction in IOP was higher, which supports the theory that CSF pressure indents the globe and leads to an increase in IOP. Although these changes in IOP are small, this study provides further evidence for a connection between IOP and CSFP.

Unilateral high-axial myopia can be associated with amblyopia and relative proptosis due to elongation of the eye and staphyloma formation. It is important to consider addressing any relative proptosis at the time of a lower eyelid blepharoplasty as the proptotic eye often creates a significant negative vector and increases the likelihood of postoperative retraction and scleral show. We present twin sisters who presented for a lower eyelid blepharoplasty evaluation; each sister had unilateral proptosis with high-axial myopia. Both underwent bilateral lower eyelid blepharoplasty and unilateral fat decompression in the proptotic eye. One sister required additional medial wall bony decompression to resolve the proptosis at the time of the aforementioned surgery. Therefore, it is important to consider globe position and degree of proptosis at the time of lower eyelid blepharoplasty surgery to optimize surgical results.

Conjunctival mucosa-associated lymphoid tissue lymphoma classically presents as a subconjunctival mass, most often in the fornix. The presence of conjunctival mucosa-associated lymphoid tissue lymphoma with spread down the nasolacrimal duct has only been reported once previously. The authors present a case of a 35-year-old woman with a right conjunctival mass in the inferior fornix along with sinus congestion and fullness. A biopsy of the conjunctival mass and the nasal turbinate revealed a conjunctival mucosa-associated lymphoid tissue lymphoma. Therefore, it is important to consider spread down the nasolacrimal duct in patients with conjunctival lymphoma also presenting with difficulty breathing or nasal congestion.

PURPOSE To evaluate the relationship between pre-Mohs skin cancer lesion measurements with the post-Mohs defect size in order to most accurately estimate post-Mohs defect size. METHODS This is a retrospective analysis of patients who underwent Mohs excision by one of 3 Mohs surgeons followed by reconstruction for basal cell carcinoma or squamous cell carcinoma of the eyelid. The study included all patients from January 2011 to May 2018 operated on by a single oculoplastic surgeon (R.M.) at the University of Texas Southwestern Medical Center. Maximum horizontal and vertical (H/V) dimensions were determined clinically by Mohs surgeons at the time of excision and photographs of the lesion and defect size were analyzed in order to determine the total area of the lesion preoperatively and the defect postoperatively with Image J using H/V dimensions and the area tracing function. RESULTS Forty-two patients with periocular skin cancers underwent Mohs resection followed by reconstruction. The Mohs defect was overall 4.88 times the size of the preoperative skin cancer measurement using maximum H/V dimensions by Mohs surgeons (p < 0.0001). When using Image J, the area of the Mohs defect was 6.5 times the size of the preoperative lesion (p < 0.0001) using both the maximum H/V dimensions and the area tracing function. There was a statistically significant difference between the Image J area tracing and area determined with H/V dimensions by both the Mohs surgeon and Image J. CONCLUSIONS Postoperative Mohs defect size can be estimated based on maximum H/V dimensions clinically or with Image J technology. Image J digital photograph analysis using the area tracing function more accurately determines the pre-Mohs lesion size and the post-Mohs defect area when compared with standard maximum H/V measurements and digital photographic analysis of maximum H/V measurements with Image J.The preoperative periocular skin cancer measurements can assist in determining the post-Mohs defect size.

To analyze the conjunctival changes, especially goblet cell populations, following Muller's muscle conjunctival resection (MMCR) by histologically evaluating pre and post-MMCR specimens.This is a retrospective analysis of conjunctival samples sent for histologic evaluation from two patient populations: those who had previously undergone a MMCR and required repeat surgery and controls who underwent a MMCR surgery in a previously unoperated eyelid. Specimens underwent hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) staining to accentuate goblet cell identification and were evaluated by two ocular pathologists to quantify goblet cell populations and note other anatomical changes. Statistical analysis of goblet cell populations was then performed.Four samples were identified for each group: (1) post-MMCR and (2) control. The mean age was 67 years in the post-MMCR group and 66 years in the control group. The mean goblet cell population was 7 ± 5 cells/mm in the post-MMCR conjunctiva and was 39 ± 16 cells/mm in the control group, which was statistically significant (p = 0.01). Samples from both groups demonstrated scarring and inflammatory cell infiltrate.While there was a relative loss of goblet cell populations in the conjunctiva overlying the region of surgery following MMCR, the lack of dry eye symptoms or changes in tear production reported in prior studies suggests that there may be enough goblet cell population reserve in the remaining accessory lacrimal glands and in the unaltered conjunctiva to provide sufficient lubrication and ocular protection.

Purpose To describe a reversible syndrome of epiphora, functional punctal stenosis, and chronic pretarsal conjunctivitis associated with corticosteroid or corticosteroid-antibiotic eyedrop use. Methods This is an Institutional Review Board-approved retrospective review of patients diagnosed with epiphora, punctal stenosis, and chronic conjunctivitis by a single surgeon (B.J.W.). These patients were subsequently invited to participate in a prospective study involving allergy skin patch testing for ophthalmic drops, common excipients, and active ingredients. Results Thirteen patients received a diagnosis of punctal congestion syndrome. The average age was 63 years (range, 41-93) and 69.2% were female. Findings were bilateral in 61.5%. All had used preserved drops in the affected eye(s). Various antecedent diagnoses resulted in treatment with preserved drops. Patients experienced epiphora for an average of 3.8 months (median, 3 months; mode, 3 months; range, 1-8 months) prior to presentation. Two patients had undergone punctoplasty which failed to resolve symptoms. 92.3% of patients had been taking tobramycin-dexamethasone drops, loteprednol drops, or a combination of both prior to presentation. All were taken off preserved drops. 69.2% were also treated with a preservative-free loteprednol etabonate 0.5% ophthalmic ointment taper. All improved. Partial relief of symptoms was achieved by an average of 1.6 months (median, 2 months; mode, 2 months; standard deviation, ±0.7 months) and resolution of symptoms by 2.5 months (median, 2 months; mode, 2 months; standard deviation, ±1.7 months). One patient underwent patch testing with strong positive reactions to formaldehyde and neomycin and a weak positive reaction to gentamicin. Conclusions Functional punctal stenosis is associated with topical ophthalmic preparations, especially preserved corticosteroids and antibiotic-corticosteroid combinations. Treatment consists of removal of all preserved eyedrops. Symptoms often improve over several months.

Epiphora from monocanalicular obstruction is commonly treated with canaliculoplasty, with or without dacryocystorhinostomy, or with conjunctivodacryocystorhinostomy with Jones tube placement. We describe two patients with epiphora due to isolated monocanalicular obstruction without concurrent nasolacrimal duct obstruction who underwent endoscopic dacryocystorhinostomy; both cases had previously failed canaliculoplasty, and both reported significant improvement in epiphora postoperatively. We hypothesize this is due to decreased resistance through the lacrimal drainage system allowing for increased flow through the patent canaliculus and shortened lacrimal apparatus. In patients presenting with epiphora secondary to isolated monocanalicular obstruction, endoscopic dacryocystorhinostomy may be considered in the absence of nasolacrimal duct obstruction before proceeding to conjunctivodacryocystorhinostomy and Jones tube placement.

To evaluate the change in lateral canthal angle (LCA), inferior ocular surface exposed (IOSE), lower eyelid curvature, and margin-to-reflex distance 2 in those undergoing lower eyelid ectropion repair using a lateral tarsal strip technique.This is an Institutional Review Board-approved retrospective analysis of patients undergoing lower eyelid ectropion repair. This study included all patients from 2012 to 2018 operated on by a single surgeon at the University of Texas Southwestern Medical Center. For each patient, LCA, IOSE, and eyelid curvature were measured on preoperative and postoperative photographs using NIH Image J photographic analysis. These measurements were compared using paired 1-tail t-tests for LCA and IOSE and paired 2-tail t-tests for eyelid curvature. This study was Health Insurance Portability and Accountability Act-compliant with protection of individually identifiable information.Fifty-one patients with lower eyelid ectropion underwent lower eyelid ectropion repair using a lateral tarsal strip technique. Forty-three of the patients underwent a bilateral lower eyelid ectropion repair. There was no statistically significant difference in the LCA. There was a reduction in IOSE among both cohorts. The fourth degree polynomial trendlines generated to assess eyelid curvature demonstrated statistical significance, suggesting a flattening of eyelid curvature. margin-to-reflex distance 2 also had a statistically significant decrease postoperatively.Lower eyelid ectropion repair using a lateral tarsal strip approach causes a reduction in IOSE, a more gradual lower eyelid curvature, and a decrease in margin-to-reflex distance 2 without causing a statistically significant change in LCA.

The management of cicatricial ectropion resulting from epidermal growth factor receptor (EGFR) inhibitors is unclear. We describe two cases of bilateral cicatricial ectropion following the use of an EGFR inhibitor who were treated with oral doxycycline, topical ophthalmic steroid and antibiotic ointment to the eyelids, and topical facial steroid cream with lubrication. The first case resolved with discontinuation of panitumumab infusions along with institution of the aforementioned regimen. However, it is unclear whether the resolution was from discontinuation of the infusions or from the instituted regimen. The second case resolved without a dose adjustment of cituximab. This case may provide support for the use of this regimen prior to discontinuation of the offending agent, as there was a successful outcome without alteration of the infusions. Additional cases are necessary to determine if this is a successful means of treating bilateral lower-lid cicatricial ectropion from EGFR inhibitors.

Reconstruction of the orbital rim and floor following tumor excision is traditionally performed with bone grafts, vascularized grafts, or free flaps. The authors describe a case of an osteosarcoma of the maxillary sinus and a second case of an ossifying fibroma of the orbital floor, both of which required reconstruction of the orbital floor and rim. In both of these cases, reconstruction of the orbital floor and rim was performed with a titanium implant whose anterior portion was bent inferiorly to recreate the orbital rim. Acellular dermis was sutured over the anterior portion of the orbital implant to act as a barrier between the implant and the overlying eyelid tissues.

Purpose To analyze and quantify the characteristics and parameters of the eyelid and adnexa of males and females and correlate these findings to an aesthetically pleasing score. Methods This is an Institutional Review Board approved study involving healthy male and female volunteers. The margin-to-reflex distance, palpebral fissure, inferior scleral show, tarsal platform show, and brow fat span were measured using Image J digital photographic analysis and the images were scored by 110 non-ophthalmologists. The eyelid parameters were compared between the groups with Student t tests and the total aesthetic score was correlated to the measured parameters with Pearson's correlation coefficients (r). This study was HIPAA-compliant with protection of individually identifiable information. Results Twenty male and 22 female participants were included and divided into 2 groups based on the aesthetic score. The average aesthetic score was 3.06 for males and 3.36 for females. None of the eyelid parameters were found to be significantly significant between the 2 male groups. In females, both inferior scleral show and tarsal platform show were significantly lower in the more aesthetic group. A greater margin-to-reflex distance correlated with increased aesthetic appeal. The ratio of brow fat span/tarsal platform show was not significantly different between the 2 female groups. Conclusions Quantifying goals are important for the surgical and nonsurgical management of the eyelid and periorbita. Beauty is considered to be subjective and is comprised of various criteria. However, this study reveals that the female sex may have certain quantifiable goals for eyelid parameters that are considered more aesthetically pleasing.

Limited research exists regarding proximity of vehicles to “vulnerable road users” and effects of “conspicuity equipment”. Previous studies stated over 60% of horse/rider combinations experience near-miss traffic collisions in any one year, whereas use of fluorescent/reflective (FR) equipment did not decrease occurrences. Similarly, research into vehicle proximity to bicycles reported no significance in cyclists wearing FR. This study undertook a similar field experiment using a horse/rider combination wearing different conspicuity equipment to test proximity distance. Two horses with similar height, age, base coat color, and temperament were ridden using four conspicuity measures 60 times each (n = 240) along a straight 0.8 km lane. Measures were chosen by random crossover with two selected for each separate trip. These were an FR “tabard”, a novel black/white pattern (BW), flashing lights on a helmet (L), and control of mid-blue (C). A novel proximity meter was used on the saddle pommel and distance/approach either front or rear were logged into a voice recorder. Analysis reported a significant difference between all measures and proximities observed (P = .000). Mann–Whitney tests concluded significant differences in proximity in C versus L and BW (P = .000; P = .000), respectively. FR versus C showed no significant difference in proximity (P = .005). L versus BW reported no significant difference in proximity (W = 3640.0, P = .958). Results may suggest wearing conspicuity equipment of L or BW outperforms both C and FR. Further study is recommended to test these findings, and it is pertinent to still consider suggesting the use of FR equipment due to previous positive findings with other road users.

Foreign-body granuloma formation following filler injections is most commonly seen with permanent fillers; these reactions can occur years following the injections and often require either an intralesional steroid injection or surgical excision. The authors present a case of a 75-year-old woman with a history of systemic sarcoidosis previously treated with numerous immunosuppressive medications who was examined for bilateral infraorbital nodules and swelling that were unresponsive to treatment. She underwent a bilateral anterior orbitotomy through a transconjunctival approach with mass excision. The histologic analysis was consistent with foreign-body granulomata juxtaposed to implantable material, specifically ArteFill, which was injected many years prior. There were no separate noncaseating granulomas to suggest sarcoidosis as the underlying etiology. It is important to consider prior filler injections in patients with sarcoidosis who present with subcutaneous nodules as this changes management and may prevent the need for more aggressive immunosuppressive treatment.

The experience of Nazi occupation during the Second World War was the formative moment in the German—Alsatian and Franco-Alsatian relationship. National Socialist administrators fundamentally transformed the parameters of belonging in the province and introduced a previously unexperienced level of coercion and violence to the reordering of the borderland’s population. The Nazi administration’s conscious abandonment of any semblance of conciliatory action was particularly striking. There were to be no half-measures. Alsatians would or would not be completely German and treated as such. Yet the German occupation of Alsace during World War II was marked by both difference and continuity with previous sovereignty transfers that had occurred in 1871 and 1918. This chapter will examine post-armistice population policies, citizenship laws, and military service requirements to demonstrate that Nazi actions and policies in Alsace are better understood as representing an intensification of earlier imperial and French programs rather than a drastic break with the past.

Dermoid cysts in the orbit classically present in children as a mass in the superotemporal or superonasal orbit along the zygomatico-frontal or fronto-ethmoidal suture lines. The presence of a dermoid cyst in the superficial eyelid, not associated with the tarsus, has only been reported once previously. The authors present a case of a 60-year-old man with a painless right lower eyelid mass inferonasally that was completely excised and found to be a dermoid cyst. The presence of a dermoid cyst involving the superficial lower eyelid is very rare. Furthermore, dermoid cysts in adults typically present in the setting of trauma, which was absent in this case. Therefore, it is important to consider dermoid cysts in the differential diagnosis of eyelid lesions in adults.

Detection of wooden foreign bodies within the orbit can be difficult on imaging, including computed tomography (CT). When visible, wood appears iso- or hypodense and can mimic air or fat. We report the case of a 3-year-old boy with progressive orbital cellulitis following a penetrating wood injury to the right lower lid. CT imaging revealed a linear hyperdensity contiguous with an orbital abscess. He underwent a right anterior orbitotomy with abscess drainage, during which exploration revealed a 2.3 cm retained wooden foreign body. The appearance of wood as hyperdense on imaging is unusual. In the appropriate context, high clinical suspicion for retained wood should be maintained with any irregularity on CT imaging.

In April 1947, a mass grave containing the bodies of 11 Alsatians executed by the Offenburg Gestapo in December 1944 was uncovered in Rammersweier. In the following days, the bodies were exhumed, placed in coffins and, after a two day vigil by local residents, solemnly and publically reburied after a two confessional service in the presence of school children and a wide cross-section of local and state authorities. A roadside memorial was constructed for the victims in 1948. The bodies of the murdered Alsatians played a central symbolic role throughout the process of exhumation, commemoration, and response to the later vandalism of the erected monument in their name. This chapter argues that the meticulous attention to the remembrance activities surrounding the reburial and memorialisation of the Alsatians and the intensity of the vandalism investigation demonstrates that Badenese officials were convinced that their responses contained a symbolic resonance beyond giving eleven more victims of Nazi terror a proper burial. In effect, contemporary Badenese authorities and their Alsatian counterparts came to view the dead bodies as representative of the larger crimes of the Nazi regime, particularly those perpetrated against the population of Alsace.

War enthusiasm and the ‘stab-in-the-back’ legend (Dolchstosslegende) were cornerstones of the Interwar political right's memory of the 1914–1918 conflict and are familiar topics to any student with...

Objectives To define disease activity levels, minimal clinically important improvement (MCII) and patientacceptable symptom state (PASS) with the primary Sjögren's syndrome (SS) disease activity indexes: European League Against Rheumatism (EULAR) SS disease activity index (ESSDAI) and EULAR SS patientreported index (ESSPRI). Methods For 790 patients from two large prospective cohorts, ESSDAI, physician evaluation of disease activity, ESSPRI and patients' satisfaction with their current health status were recorded. Receiver operating characteristic curve analyses and anchoring methods were used to estimate disease activity levels of ESSDAI and the PASS of ESSPRI. At follow-up visit, patients and physicians assessed, respectively, whether symptoms and disease activity have improved or not. An anchoring method based on this evaluation was used to estimate MCII of ESSDAI and ESSPRI. Results Low-activity (ESSDAI

Background This study was conducted to assess the health status and safety practices among year-round adult farm workers and residents and included a telephone interview survey of 1,727 persons from 552 farms. Methods Logistic regression was used to analyze four safety questions. Results Among 541 farm owner/operators significant predictors of making substitutions in the use of chemicals and major changes to equipment include younger age, more persons assisting on the farm, and higher gross sales. Having training is associated with having more than a high school education. Among all participants the perception that personal protective equipment are useful is associated with being younger, male, an owner/operator or worker, and having at least a high school education. Conclusions These findings suggest that older and less educated farmers should be targeted for health and safety programs. Am. J. Ind. Med. 38:71–81, 2000. © 2000 Wiley-Liss, Inc.

The syntheses of 3,6-anhydro-1-deoxy-3-C-ethoxycarbonylmethyl- (4) and 3-C-(2-hydroxyethyl)nojirimycin (5) from 5-azido-6-O-tert-butyldiphenylsilyl-5-deoxy-1,2-O-isopropylidene-α-D-glucofuranose (8) are described. The key intermediate is 5-azido-6-O-tert-butyldiphenylsilyl-3,5-dideoxy-3-C-ethoxycarbonylmethylene-1,2-O-isopropylidene-α-D-ribo-hex-3-enofuranose (11) which was obtained by condensation of 5-azido-6-O-tert-butyldiphenylsilyl-5-deoxy-1,2-O-isopropylidene-α-D-ribo-hexos-3-ulofuranose (10) with (ethoxycarbonylmethylene)triphenylphosphorane. Conventional benzoylation of 4 resulted in the formation of the lactones 13a and 13b. The 3-C-(2-hydroxyethyl) analogue (5) was synthesized by lithium aluminum hydride reduction of 3,6-anhydro-5-azido-5-deoxy-3-C-ethoxycarbonylmethyl-1,2-O-isopropylidene-α-D-glucofuranose (12), followed by deacetalation, and hydrogenation. 3,6-Anhydro- 1 -deoxy- 3 -C-ethoxycarbonylmethyl- and 3 -C-(2-hydroxyethy1)nojirimycin derivatives, Part 4. For Part 3 see ref 3. ...

Local government’s need for accurate assessments and projections of the fiscal consequences of development is well established and persistent. This analysis demonstrates the use of a geographic information science-based planning support system to project residential growth and the fiscal consequences of development. The cornerstone of the analysis is a spatial index of urban form which captures clustering and dispersion of the built environment. A regression model indicates the spatial index to be a statistically significant determinant of expenditures on policing services in the study area. Modelled future growth was spatially and temporally disaggregated to indicate future residential growth at different planning horizons. Spatial indices were calculated for these planning horizons and incorporated into the econometric model for ceteris paribus evaluation of the effect of change in urban form on public service expenditures. Results demonstrate planning informed by PSS modelling has the potential to realize savings on public service expenditures.

State, territorial and local health departments have responsibility for all three of the HIV/AIDS Prevention Research Synthesis (PRS) project's intervention categories: behavioral, social, and policy. These health departments may be aided by the PRS project in a number of ways. These ways include the provision of information on scientifically proven interventions; the determination of sociodemographic categories underrepresented in research; the promotion of consistent methodologies and standards for reporting findings; and the fostering of greater engagement with HIV prevention research among program staff. Further development of the PRS project can enhance and expand these benefits, although the project must be sure to keep practical applications in mind.

The Online Financial Transaction (OFT) services landscape has grown with the widespread commoditization of e-commerce. Though developed for legitimate commercial means, new technologies have created many ways to anonymously transfer funds over communication networks. Law enforcement agencies now face a unique and nearly insurmountable problem: cybercriminals are able to anonymously exchange financial resources and goods, hiding virtually all traces of evidence in a complex web of financial services. Consequently, OFTs pose a significant risk to law enforcement and intelligence agencies because such anonymous transactions have become difficult to monitor and provide new opportunities to the criminals who threaten our physical world. The focus of this capstone project was to increase the understanding of anonymous OFTs using a three step approach. The first step involved developing a standardized identity framework to classify levels of anonymity in online transactions. The second step was the creation of a comprehensive database of OFT services and the information each of these services collects during individual transactions. This database incorporates the Identity Elements framework and stores relationships between OFTs. This information is then used by a suite of client applications, the third step in our approach, to analyze financial transactions. Overall, the combination of an identity framework and analytic tools forms a better understanding of the potential threats posed by dynamic anonymous technologies, and is intended to grow to function as an active method used to catch and monitor criminals.