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ABSTRACT The close relation between ground-based TeV observations and satellite borne γ-ray measurements has been important for the understanding of blazars. The observations which involve the TeV component in blazar studies are reviewed. [ABSTRACT FROM AUTHOR]

Purpose: To determine the choroidal thickness (CT) profile in keratoconus (KC) patients using swept-source optical coherence tomography (SS-OCT)., Methods: This was a prospective, cross-sectional study. One hundred two eyes of 52 KC patients were studied using Pentacam and SS-OCT. The macular CT profile was created by manually measuring the distance between the retinal pigment epithelium and the choroid-sclera junction on horizontal b-scans at nine different macular locations. The results were compared to 93 eyes of 93 healthy controls., Results: Mean age of the KC group was 34.9 ± 13.5 years and mean axial length (AL) was 24.1 ± 1.3 mm. Mean topographic KC classification (TKC) was 2.0; 39 eyes were classified as early KC (TKC <1-2), 34 eyes as moderate (TKC 2, 2-3), and 29 as advanced (TKC 3+). Mean subfoveal CT was 383.2 μm in KC patients and 280.5 μm in control group ( P < 0.001). CT in KC patients was statistically thicker in all measure locations ( P < 0.001). CT in KC eyes decreased with age, approaching control group at >45 years old, losing statistical significance ( P = 0.37)., Conclusions: CT in KC patients is statistically thicker than in healthy population. After age 45, CT decreases approaching control group values., Translational Relevance: This study describes changes in the CT profile of KC patients, a disease that was considered purely corneal. These choroidal changes argue that KC is a disease that likely involves several ocular structures other than the cornea, and could open new research lines related to the pathophysiology of KC.

Introduction. Clotiapine is an atypical antipsychotic of the dibenzothiazepine class introduced in a few European countries since 1970, efficient in treatment-resistant schizophrenic patients. There is little published data on the therapeutic and toxic concentrations of this drug. Aims. The aim of the present study is the development and validation of a method that allows the detection and quantification of clotiapine in blood and urine specimens by gas chromatography-mass spectrometry (GC-MS). Methods. Validation was performed working on spiked postmortem blood and urine samples. Samples were extracted with liquid-liquid extraction (LLE) technique at pH 8.5 with n-hexane/dichloromethane (85/15 v/v) and analysis was followed by GC-MS. Methadone-d9 was used as internal standard. Results. The limit of detection (LOD) was 1.2 and 1.3 ng/mL for urine and blood, respectively, while the lower limit of quantification (LLOQ) was 3.9 and 4.3 ng/mL, respectively. Linearity, precision, selectivity, accuracy, and recovery were also determined. The method was applied to a postmortem case. The blood and urine clotiapine concentrations were 1.32 and 0.49 μg/mL, respectively. Conclusions. A reliable GC-MS method for the detection and quantification of clotiapine in blood and urine samples has been developed and fully validated and then applied to a postmortem case.

RNA interference by feeding worms bacteria expressing dsRNAs has been a useful tool to assess gene function in C. elegans. While this strategy works well when a small number of genes are targeted for knockdown, large scale feeding screens show variable knockdown efficiencies, which limits their utility. We have deconstructed previously published RNAi knockdown protocols and found that the primary source of the reduced knockdown can be attributed to the loss of dsRNA-encoding plasmids from the bacteria fed to the animals. Based on these observations, we have developed a dsRNA feeding protocol that greatly reduces or eliminates plasmid loss to achieve efficient, high throughput knockdown. We demonstrate that this protocol will produce robust, reproducible knock down of C. elegans genes in multiple tissue types, including neurons, and will permit efficient knockdown in large scale screens. This protocol uses a commercially available dsRNA feeding library and describes all steps needed to duplicate the library and perform dsRNA screens. The protocol does not require the use of any sophisticated equipment, and can therefore be performed by any C. elegans lab.

Fatal thromboembolism during physical restraint in patients suffering from psychotic disorders is a very rare occurrence. In the case we present here, the criteria used in forensic pathology for the age determination of venous thrombi are applied to a case of pulmonary embolism in a patient suffering from schizophrenia who died after physical restraint. The possible association between conventional antipsychotic drugs and deep venous thrombosis, followed by pulmonary embolism, in a man with no predisposing risk factors, as well as the question concerning the appropriateness of medical care, are discussed.

Dopamine signaling modulates voluntary movement and reward-driven behaviors by acting through G protein-coupled receptors in striatal neurons, and defects in dopamine signaling underlie Parkinson's disease and drug addiction. Despite the importance of understanding how dopamine modifies the activity of striatal neurons to control basal ganglia output, the molecular mechanisms that control dopamine signaling remain largely unclear. Dopamine signaling also controls locomotion behavior in Caenorhabditis elegans. To better understand how dopamine acts in the brain we performed a large-scale dsRNA interference screen in C. elegans for genes required for endogenous dopamine signaling and identified six genes (eat-16, rsbp-1, unc-43, flp-1, grk-1, and cat-1) required for dopamine-mediated behavior. We then used a combination of mutant analysis and cell-specific transgenic rescue experiments to investigate the functional interaction between the proteins encoded by two of these genes, eat-16 and rsbp-1, within single cell types and to examine their role in the modulation of dopamine receptor signaling. We found that EAT-16 and RSBP-1 act together to modulate dopamine signaling and that while they are coexpressed with both D1-like and D2-like dopamine receptors, they do not modulate D2 receptor signaling. Instead, EAT-16 and RSBP-1 act together to selectively inhibit D1 dopamine receptor signaling in cholinergic motor neurons to modulate locomotion behavior.

Purpose: Descemetocele is a severe complication of corneal ulceration associated with a high risk of perforation. We describe a modified air-assisted deep anterior lamellar keratoplasty (DALK) technique for the surgical management of small and large epithelialized descemetoceles., Methods: Two representative cases are presented, one with a small (2 mm) and one with a large (4 mm) descemetocele. In both cases, the air-assisted lamellar dissection allowed a superficial keratectomy and access to the Descemet membrane. Viscoelastic was then directly injected through the stromal hole to separate the Descemet membrane from the posterior stroma, thereby allowing its complete removal., Results: DALK was successfully performed using this modified air-assisted DALK technique. Visual acuity improved from counting fingers and hand motion to 20/40 and was maintained for at least 1 year after surgery., Conclusions: These cases demonstrate that the modified air-assisted DALK technique may be proposed for the management of small and large descemetoceles, allowing both tectonic and visual rehabilitation.

Purpose: To assess corneal epithelial cell survival after keratoplasty., Methods: Corneal impression cytology (CIC) was performed on sex-mismatched corneal transplants. Fluorescent in situ hybridization (FISH) with sex chromosome-specific probes was performed to identify epithelial cell mosaicism and therefore allocate the donor or recipient origin of the cells. Twenty-four samples of corneal epithelial cells derived from 21 transplanted patients were analyzed. All patients received post-operative treatment using dexamethasone eye drops, with progressive tapering over 18 months, and nine patients also received 2% cyclosporine eye drops., Results: Out of the 24 samples reaching quality criteria, sex mosaicism was found in 13, demonstrating the presence of donor-derived cells at the center of the graft for at least 211 days post keratoplasty. Kaplan-Meier analysis established a median survival of donor corneal epithelial cells of 385 days. Although not statistically significant, the disappearance of donor cells seemed to be delayed and the average number of persistent cells appeared to be greater when 2% cyclosporine was used topically as an additional immunosuppressive therapy., Conclusions: The combination of corneal impressions and FISH analysis is a valuable tool with negligible side effects to investigate the presence of epithelial cell mosaicism in sex-mismatched donor transplants. Epithelial cells survived at the center of the graft with a median survival of more than one year, suggesting slower epithelial turnover than previously described.

Recent studies suggest that p16 overexpression determined by immunohistochemistry would be a specific marker for neoplastic and dysplastic squamous cells associated with high-risk HPV. The purpose of this study was to assess the correlation between cyto-histological findings, p16 expression and HPV subtype. A total of 99 biopsies were selected, 4 endocervical curettages and 95 uterine cervix biopsies, as well as 30 cervicovaginal smears from other 30 patients. The samples were divided according to the morphological diagnosis. Paraffin-embedded sections and cervicovaginal smears were immunostained using the CINtec p16INK4a Cytology Kit (DAKO). HPV was analyzed by PCR in 25 of the 99 biopsies with low-grade squamous intraepithelial lesion. Among those patients with neither HPV nor dysplasia, 1 of 35 (2.9%) biopsies and 1 of 11 (9%) smears were positive for p16. Sixteen of 25 (64%) biopsies and 6 of 10 (60%) smears of the low-grade lesion cases, and 38 of 39 (97.4%) biopsies and 8 of 9 (89%) smears of the high-grade lesion and squamous carcinoma were positive for p16. All cases of HPV-6/11 were negative or focally positive for p16. Most cases of HPV-18 or other subtypes were diffusely positive. Our results indicate that p16 expression is highly correlated with cyto-histological diagnosis, and is associated with diffuse staining and high-risk HPV. This technique provides greater objectivity in doubtful cases, and helps select patients at risk of disease progression at an acceptable cost when used in large populations.

Purpose: We report an unusual increase in the number of cases of keratomycosis attributable to Fusarium solani in contact lens wearers., Design: Observational case series., Methods: Between November 2005 and May 2006, 14 corneal abscesses were reported at the University Hospital Center of Fort-de-France. Twelve patients were contact lens wearers, and 10 used Bausch & Lomb (Rochester, New York, USA) ReNu with MoistureLoc. Corneal scrapings were collected for microbiological analyses., Results: In six months, five abscesses attributable to Fusarium solani in contact lens wearers, using Bausch & Lomb ReNu with MoistureLoc as contact lens solution, were reported., Conclusions: This study reports an epidemic of keratomycosis attributable to Fusarium solani among contact lens wearers in the Caribbean, during the same timeframe as a similar epidemic in Asia and North America. We are unaware of previous report of this phenomenon and could find no reference to it in a computerized search utilizing MEDLINE.

The average mass composition of cosmic rays with primary energies between 10(17) and 10(18) eV has been studied using a hybrid detector consisting of the High Resolution Fly's Eye (HiRes) prototype and the MIA muon array. Measurements have been made of the change in the depth of shower maximum and the muon density as a function of energy. The results show that the composition is changing from a heavy to lighter mix as the energy increases.

We present X-ray observations of the BL Lacertae object Mrk 501 that were taken with the Rossi X-Ray Timing Explorer in 1998 May as part of a multiwavelength campaign. The X-ray light curve shows a very rapid flare in which the 2-10 keV flux increased by approximately 60% in less than 200 s. This rapid rise is followed by a drop-off in the 2-10 keV flux of approximately 40% in less than 600 s. The 10-15 keV variation in this flare is roughly a factor of 2 on similar timescales. During the rise of the flare, the 3-15 keV spectral index hardened from 2.02+/-0.03 to 1.87+/-0.04, where it remained during the decay of the flare. This is the fastest variation ever seen in X-rays from Mrk 501 and among the fastest seen at any wavelength for this object. The shift in the energy at which the spectral power peaks (from less, similar3 keV before the flare to greater, similar30 keV during the flare) is also among the most rapid shifts seen from this object. This flare occurs during an emission state (2-10 keV flux approximately 1.2x10-10 ergs cm-2 s-1) that is approximately 25% of the peak flux observed in 1997 April from this object but that is still high compared to its historical average X-ray flux. The variations in the hardness ratio are consistent with the low-energy variations leading those at high energies during the development and decay of the flare. This pattern is rare among high-frequency peaked BL Lac objects like Mrk 501, but has been seen recently in two other TeV-emitting BL Lac objects, Mrk 421 and PKS 2155-304. The hard lag is consistent with a flare dominated by the acceleration timescale for a simple relativistic shock model of flaring.