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Introduction: Patients with the acquired immunodeficiency syndrome (AIDS) have an increased prevalence and incidence of intermediate-stage age-related macular degeneration (AMD). Several elevated plasma inflammatory biomarkers are associated with increased incidence of intermediate-stage AMD in this population. We evaluated the association between AMD risk alleles and plasma inflammatory biomarker levels in persons with AIDS. Materials and Methods: Cryopreserved plasma specimens of 229 non-Hispanic White and 252 non-Hispanic blacks from the Longitudinal Study of the Ocular Complications of AIDS cohort were assayed for plasma levels of soluble tumor necrosis factor receptor (sTNFR) 2, interleukin (IL)-18, C × 3motif chemokine ligand 1 (CX3CL1), C-reactive protein (CRP), and soluble CD14 (sCD14). Genotyping included AMD-associated variants rs10801553 and rs800292 for complement factor H (CFH) rs9332739 and rs547154 for complement factor 2 (C2), rs2230199 for C3, rs2285714 for CFI, and rs3732379 and rs3732378 for C × 3motif chemokine receptor 1 (CX3CR1). Results: In Whites, AMD low-risk CX3CR1 variants (V249I and T280M) were associated with reduced plasma levels of IL-18. In Blacks, AMD low-risk C3 R102G and low-risk CX3CR1 T280M variants were associated with reduced CRP levels. Conclusions: Genetic variants in AMD-associated immune genes may influence AMD-associated systemic plasma inflammatory biomarker levels in patients with AIDS. [ABSTRACT FROM AUTHOR]

Up to 8% of cisgender women meet diagnostic criteria for Female Sexual Interest/Arousal Disorder (SIAD), a diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, yet treatment research for SIAD remains scarce, particularly for transgender women and non-binary individuals. The treatment relevance of the Approach-Avoidance Motivation Model for SIAD was tested in a sample of cis- and transgender women, and non-binary individuals, who either met criteria for SIAD (n = 45) or reported no sexual concerns (n = 76). Participants completed an online writing exercise previously found to increase the salience of approach or avoidance sexual motivation, or a control writing task. At baseline, and 72 hours following the writing task, they completed measures of sexual motivation, sexual desire, and partnered sexual behaviors. Participants with SIAD in the approach condition significantly increased in approach sexual motivation immediately following the manipulation but these improvements were not maintained 72 hours later. Compared to baseline, participants who wrote about an approach-motivated sexual encounter experienced a decrease in sexual desire and partnered sexual behaviors, while participants who wrote about an avoidance-motivated sexual encounter had decreased motivation but increased partnered sexual behaviors 72 hours following the manipulation. Overall, findings did not show support for the relevance of the approach-avoidance motivation manipulation for SIAD. Future studies might explore novel ways of targeting sexual motivation to address sexual difficulties. [ABSTRACT FROM AUTHOR]

Virtual Reality (VR)-based treatments for anxiety disorders are efficacious but there is a lack of research examining anxious responses to VR erotica, which could innovate treatments for sexual difficulties. We examined erotica features that elicited anxiety and sexual presence in women. Thirty-eight women viewed erotic videos from different modalities (2D, VR) and points of view (1st, 3rd person) and completed anxiety and sexual presence measures before and after each video. Women experienced greater anxiety for VR than 2D films and reported the most anxiety for VR 1st person films. Sexual presence was affected by modality and point of view. [ABSTRACT FROM AUTHOR]

Approximately 1 in 3 women experience low sexual desire. Despite this being a common concern, many women never seek professional help for their difficulties and will instead turn to online resources for information. We sought to address this need for digitally-accessible, evidence-based information on low sexual desire by creating a social media Knowledge Translation (KT) campaign called #DebunkingDesire. Our team led a 10 month social media campaign where our primary outcomes for the campaign were impressions, reach, and engagement. We generated over 300,000 social media impressions; appeared on 11 different podcasts that were listened to/downloaded 154,700 times; hosted and participated in eight online events; and attracted website users from 110 different countries. Over the course of the campaign we compiled lessons learned on what worked for disseminating our key messages and the importance of creating community for this population. These findings point to the utility of using social media as part of KT campaigns in sexual health, and to the importance of collaborating with patient partners and considering social media ads and podcasts to meet reach goals. [ABSTRACT FROM AUTHOR]

Sexual Interest/Arousal Disorder (SIAD) is a common sexual dysfunction in women. Both mindfulness-based cognitive therapy (MBCT) plus psychoeducation and sex therapy, education, and support (STEP; which contains the same educational information as in the MBCT arm but also integrates supportive-expressive therapy), are effective. We tested mediators and moderators of improvements. Each treatment arm consisted of eight sessions delivered weekly, and participants completed measures online pre-treatment, immediately post-treatment, and at 6- and 12-month post-treatment. Depression, self-reported interoceptive awareness, self-compassion, self-criticism, and mindfulness were examined as mediators, and expectations for improvement as a moderator. Of 148 cisgender women who consented, 70 were randomized to the MBCT plus psychoeducation group (mean age 39.3 ± 13.2 yrs) and 78 to the STEP group (mean age 37.9 ± 12.2 yrs). Decreases in depression mediated decreases in sexual distress in the MBCT plus psychoeducation group only. Improvements in interoceptive awareness mediated changes in both sexual desire and arousal, and sexual distress, and to a greater degree after MBCT plus psychoeducation. Changes in self-compassion mediated changes in sexual desire and arousal only for the MBCT plus psychoeducation group and mediated changes in sexual distress in both groups. Reductions in self-criticism mediated improvements in sexual distress to a greater extent after MBCT plus psychoeducation. Changes in mindfulness predicted changes in desire and arousal, and distress only in the MBCT plus psychoeducation group. Expectations for improvement did not moderate any outcomes. The findings have implications for understanding common and potentially distinct pathways by which MBCT plus psychoeducation and supportive sex education improve symptoms of SIAD. [ABSTRACT FROM AUTHOR]

We examined changes in frequency of sexual behaviors, dyadic sexual desire, relationship satisfaction, and COVID-19 stress in Canadians across the pandemic, considering partner status. Participants completed online questionnaires. Participants with live-in partners and single participants decreased in dyadic sexual behaviors. In August–September 2020, participants with live-in partners engaged in more dyadic sexual behaviors than single participants. In November 2021, all partnered participants engaged in more dyadic sexual behaviors than single participants. Decreases in COVID-19 stress were observed. Findings suggest that despite decreases in COVID-19 stress, there may be long-lasting pandemic impacts on sexual behaviors. [ABSTRACT FROM AUTHOR]

Degradation of macromolecules delivered to lysosomes by processes such as autophagy or endocytosis is crucial for cellular function. Lysosomes require more than 60 soluble hydrolases in order to catabolize such macromolecules. These soluble hydrolases are tagged with mannose6-phosphate (M6P) moieties in sequential reactions by the Golgi-resident GlcNAc-1-phosphotransferase complex and NAGPA/UCE/uncovering enzyme (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase), which allows their delivery to endosomal/lysosomal compartments through trafficking mediated by cation-dependent and -independent mannose 6-phosphate receptors (MPRs). We and others recently identified TMEM251 as a novel regulator of the M6P pathway via independent genome-wide genetic screening strategies. We renamed TMEM251 to LYSET (lysosomal enzyme trafficking factor) to establish nomenclature reflective to this gene's function. LYSET is a Golgi-localized transmembrane protein important for the retention of the GlcNAc-1-phosphotransferase complex in the Golgi-apparatus. The current understanding of LYSET's importance regarding human biology is 3-fold: 1) highly pathogenic viruses that depend on lysosomal hydrolase activity require LYSET for infection. 2) The presence of LYSET is critical for cancer cell proliferation in nutrient-deprived environments in which extracellular proteins must be catabolized. 3) Inherited pathogenic alleles of LYSET can cause a severe inherited disease which resembles GlcNAc-1-phosphotransferase deficiency (i.e., mucolipidosis type II). Abbreviations: GlcNAc-1-PT: GlcNAc-1-phosphotransferase; KO: knockout; LSD: lysosomal storage disorder; LYSET: lysosomal enzyme trafficking factor; M6P: mannose 6-phosphate; MPRs: mannose-6-phosphate receptors, cation-dependent or -independent; MBTPS1/site-1 protease: membrane bound transcription factor peptidase, site 1; MLII: mucolipidosis type II; WT: wild-type [ABSTRACT FROM AUTHOR]

We evaluated various facets of sexual health in Canadians across phases of the COVID-19 pandemic. Online questionnaires every four weeks from April–August 2020. Higher COVID-19 stress predicted higher baseline dyadic sexual desire, lower relationship satisfaction, higher desire for solitary sexual behavior, and higher likelihood of experiencing sexual coercion among people with a live-in romantic partner. Dyadic sexual desire and pandemic-related stress both decreased with time, whereas solitary sexual behavior decreased and dyadic sexual behavior increased among participants without a live-in romantic partner. Our findings reveal differential impacts of COVID-19 related stress on sexual outcomes. [ABSTRACT FROM AUTHOR]

We evaluated the associations of clinical and demographic characteristics with visual acuity (VA) with over 5 years in a subspecialty noninfectious uveitis population. Retrospective data from 5,530 noninfectious uveitis patients were abstracted by expert reviewers, and contemporaneous associations of VA with demographic and clinical factors were modeled. Patients were a median of 41 years old, 65% female, and 73% white. Eyes diagnosed ≥5 years prior to cohort entry had worse VA (−1.2 lines) than those diagnosed <6 months prior, and eyes with cataract surgery performed prior to entry had worse VA (−5.9 lines) than those performed during follow-up. Vitreous haze (−4.2 lines for 3+ vs quiet), hypotony (−2.5 lines for ≤5 mm Hg vs 6–23 mm Hg), and CNV (−1.8 lines) all were strongly associated with reduced VA. Factors associated with reduced VA included well-known structural complications, and lack of subspecialty care during cataract surgery. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated visual acuity (VA) over 5 years in a subspecialty noninfectious uveitis population.Methods: Retrospective data from 5,530 noninfectious uveitis patients with anterior, intermediate, posterior or panuveitis were abstracted by expert reviewers. Mean VA was calculated using inverse probability of censoring weighting to account for losses to follow-up.Results: Patients were a median of 41 years old, 65% female, and 73% white. Initial mean VA was worse among panuveitis (20/84) than posterior (20/64), intermediate (20/47), and anterior (20/37) uveitides. On average, mean VA improved by 0.62, 0.51, 0.37, and 0.26 logMAR-equivalent lines over 2 years, respectively (each P < .001), then remained stable, except posterior uveitis mean VA worsened to initial levels.Conclusion: Mean VA of uveitic eyes improved and, typically, improvement was sustained under uveitis subspecialty care. Because VA tends to improve under tertiary care, mean VA change appears a better outcome for clinical studies than time-to-loss of VA. [ABSTRACT FROM AUTHOR]

An international, expert led consensus initiative was set up by the Collaborative Ocular Tuberculosis Study (COTS) group to develop systematic, evidence, and experience-based recommendations for the treatment of ocular TB using a modified Delphi technique process. In the first round of Delphi, the group identified clinical scenarios pertinent to ocular TB based on five clinical phenotypes (anterior uveitis, intermediate uveitis, choroiditis, retinal vasculitis, and panuveitis). Using an interactive online questionnaires, guided by background knowledge from published literature, 486 consensus statements for initiating ATT were generated and deliberated amongst 81 global uveitis experts. The median score of five was considered reaching consensus for initiating ATT. The median score of four was tabled for deliberation through Delphi round 2 in a face-to-face meeting. This report describes the methodology adopted and followed through the consensus process, which help elucidate the guidelines for initiating ATT in patients with choroidal TB. [ABSTRACT FROM AUTHOR]

Purpose: To standardize a nomenclature system for defining clinical phenotypes, and outcome measures for reporting clinical and research data in patients with ocular tuberculosis (OTB).Methods: Uveitis experts initially administered and further deliberated the survey in an open meeting to determine and propose the preferred nomenclature for terms related to the OTB, terms describing the clinical phenotypes and treatment and reporting outcomes.Results: The group of experts reached a consensus on terming uveitis attributable to tuberculosis (TB) as tubercular uveitis. The working group introduced a SUN-compatible nomenclature that also defines disease "remission" and "cure", both of which are relevant for reporting treatment outcomes.Conclusion: A consensus nomenclature system has been adopted by a large group of international uveitis experts for OTB. The working group recommends the use of standardized nomenclature to prevent ambiguity in communication and to achieve the goal of spreading awareness of this blinding uveitis entity. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate adalimumab as an immunomodulatory treatment for non-infectious ocular inflammatory diseases.Methods: Characteristics of patients treated with adalimumab were abstracted in a standardized chart review. Main outcomes measured were control of inflammation, corticosteroid-sparing effect, and visual acuity.Results: In total, 32 patients with ocular inflammation were treated with adalimumab. The most common ophthalmic diagnoses were anterior uveitis, occurring in 15 patients (47%), and scleritis, occurring in 9 patients (28%). At 6 months of therapy, among 15 eyes with active inflammation, 7 (47%) became completely inactive, and oral prednisone was reduced to ≤10 mg/day in 2 of 4 patients (50%). On average, visual acuity decreased by 0.13 lines during the first 6 months of treatment. Adalimumab was discontinued because of lack of effectiveness in four patients within 6 months.Conclusions: Adalimumab was moderately effective in controlling inflammation in a group of highly pre-treated cases of ocular inflammatory disease. [ABSTRACT FROM AUTHOR]

The vacuolar-type H+-translocating ATPase (v-H+-ATPase) has been implicated in the amino acid-dependent activation of the mechanistic target of rapamycin complex 1 (MTORC1), an important regulator of macroautophagy. To reveal the mechanistic links between the v-H+-ATPase and MTORC1, we destablilized v-H+-ATPase complexes in mouse liver cells by induced deletion of the essential chaperone ATP6AP2. ATP6AP2-mutants are characterized by massive accumulation of endocytic and autophagic vacuoles in hepatocytes. This cellular phenotype was not caused by a block in endocytic maturation or an impaired acidification. However, the degradation of LC3-II in the knockout hepatocytes appeared to be reduced. When v-H+-ATPase levels were decreased, we observed lysosome association of MTOR and normal signaling of MTORC1 despite an increase in autophagic marker proteins. To better understand why MTORC1 can be active when v-H+-ATPase is depleted, the activation of MTORC1 was analyzed in ATP6AP2-deficient fibroblasts. In these cells, very little amino acid-elicited activation of MTORC1 was observed. In contrast, insulin did induce MTORC1 activation, which still required intracellular amino acid stores. These results suggest that in vivo the regulation of macroautophagy depends not only on v-H+-ATPase-mediated regulation of MTORC1. [ABSTRACT FROM PUBLISHER]

Purpose: To characterize nodular lesions of the retina and optic nerve with spectral-domain optical coherence tomography (SD-OCT) in patients with sarcoidosis. Methods: This is a retrospective series of 6 eyes from 5 patients with an established diagnosis of sarcoidosis, with clinically detected nodules of the optic nerve or retina. All lesions were imaged with fundus photography and SD-OCT on presentation, and followed with serial imaging after treatment with corticosteroids and/or immunomodulatory therapy. Results: Spectral OCT through the lesions revealed nodular hyperreflective processes obscuring the retinal layers or optic cup, with local structural changes, including subretinal and intraretinal fluid. After treatment with corticosteroids and/or immunosuppression in 4 followed patients, all lesions regressed with improvement in associated structural changes, but did not entirely disappear. Conclusions: Spectral OCT can be useful in identifying lesion morphology and location, and in tracking the response to treatment in eyes with posterior-segment nodules, presumably secondary to sarcoidosis. [ABSTRACT FROM AUTHOR]

Purpose: To summarize the available published data regarding the treatment of JIA-associated chronic uveitis.Methods: Available peer-reviewed publications regarding the treatments of JIA-associated uveitis were read by multiple authors (RMA, EM, JET, and DH) and the data from these reports were synthesized for this review.Results: Juvenile idiopathic arthritis (JIA)-associated chronic uveitis is a significant cause of ocular morbidity and visual impairment in children, often resulting in more frequent complications and worse visual outcomes than other types of pediatric uveitis. Since not all patients respond to the first medication introduced, it is useful to have a wide range of available treatment modalities to address recalcitrant disease. Treatment options for JIA-associated uveitis have increased substantially over the past decade, particularly with the availability of newer biological agents in addition to established medication classes such as anti-inflammatories (including topical and systemic corticosteroids) and antimetabolites.Conclusions: Although data are increasing regarding biologic agents, definitive randomized prospective clinical trials would be helpful to determine their optimal dose, frequency, treatment duration, and long-term safety in children. [ABSTRACT FROM AUTHOR]

Background: Discoid lupus erythematosus (DLE) demonstrates both cutaneous and mucosal manifestations. Mucosal involvement is typically limited to the oral and anogenital mucosa. Conjunctival involvement in DLE is rare, especially in the absence of accompanying cutaneous disease.Objective: We describe the clinical and immunopathologic features of two cases of cicatrizing conjunctivitis due to DLE.Methods: In each patient, the clinical, immunopathologic, and serologic features were reviewed and the results recorded.Results: Both patients presented with cicatrizing conjunctivitis suggestive of mucous membrane pemphigoid. Patient 1 had no history of typical DLE skin lesions. Patient 2 had a history of cutaneous and oral DLE prior to presentation. Histologic, electron microscopic, and direct immunofluorescence examination confirmed the diagnosis DLE in both patients.Conclusion: In patients presenting with cicatrizing conjunctivitis, DLE should be considered in the differential diagnosis. Performing appropriate investigations to distinguish conjunctival DLE from other autoimmune diseases with conjunctival involvement such as mucous membrane pemphigoid is critical in selecting an appropriate treatment regimen, in offering an accurate prognosis, and in monitoring for signs and symptoms of disease progression. [ABSTRACT FROM AUTHOR]

Proteins are an important class of biologics. Their higher-order structures and therefore their functions are fundamentally determined by the correct formation of disulfide bonds (DSBs), making DSB analysis a central part of their development and production. Mass spectrometry-based bottom-up approaches are most widely used and are further classified according to different methods applied for DSB cleavage. Despite the importance of DSB analysis and the wide range of available methodologies, it is often a challenging and time consuming task. However, due to the current increase in biosimilar development in which animal and clinical trials can be reduced by extensive analytical comparability studies, increased efforts are being made to simplify DSB analysis. As an example of these developments, a matrix-assisted laser desorption/ionization time-of-flight (TOF)/TOF workflow for the automated profiling and identification of DSBs is presented. Furthermore, mass spectrometry based methodologies, which do not identify DSBs directly but measure their influence on the higher-order structure, are also considered. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of macular edema on visual acuity and visual field sensitivity in uveitis. Design: This study utilized baseline data from the Multicenter Uveitis Steroid Treatment (MUST) Trial, a randomized, parallel treatment clinical trial comparing alternative treatments for intermediate, posterior and panuveitis. Patients & Methods: 255 patients (481 eyes with uveitis) recruited at 23 subspecialty centers. Visual acuity, optical coherence tomography and Humphrey 24-2 visual field testing. Results: Macular edema was associated with impaired visual acuity ( p < 0.01). Different phenotypes of macular edema were associated with different degrees of visual impairment: cystoid changes without retinal thickening were associated with moderately impaired visual acuity (-5 ETDRS letters), but visual acuity was worse in eyes with retinal thickening (-13 letters) and with both cysts and thickening (-19 letters). Uveitis sufficient to satisfy the study's inclusion criteria was associated with impaired visual field sensitivity, but eyes with macular edema had even worse visual field sensitivity ( p < 0.01). Conclusions: The observation that macular edema substantially reduces visual function suggests macular edema itself is an important endpoint to study in the treatment of uveitis. As uveitis and macular edema both impair visual field sensitivity as measured by Humphrey 24-2 perimetry, both should be considered when evaluating patients with uveitis and raised intraocular pressure for glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prevalence of hypotony in patients with severe forms of uveitis. Methods: The Multicenter Uveitis Steroid Treatment (MUST) Trial, a randomized study, enrolled 255 patients. Patients with hypotony at the baseline visit were identified. Results: Twenty (8.3%) of 240 patients with sufficient data had hypotony. Hypotony was more common in patients with uveitis ≥5 years duration (odds ratio [OR] == 5.0; p < .01), and in eyes with a history of ocular surgery (vitrectomy vs. none, OR == 3.1; p == .03). Hypotony was less in patients with older age of uveitis onset (>51 years vs. <51 years, OR == 0.1; p == .02), in Caucasian patients (OR == 0.1; p < .01) compared to African American patients. Hypotonous eyes were more likely to have visual impairment (OR == 22.9; p < .01). Conclusions: Hypotony is an important complication of uveitis and more commonly affects African-American patients, those with uveitis onset at a younger age, and those with longer disease duration. It is associated with visual impairment. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness and risk of complications of high-dose intravenous pulsed corticosteroids for noninfectious ocular inflammatory diseases. Methods: Retrospective cohort study in which 104 eyes of 70 patients who received high-dose intravenous corticosteroids for treatment of active ocular inflammation were identified from five centers. The main outcome measures were control of inflammation and occurrence of ocular or systemic complications within 1 month after treatment. Results: Within ≤1 month of starting treatment, 57% of eyes achieved complete control of inflammation (95% confidence interval (CI): 33-83%), improving to 82% when near-complete control was included (95% CI: 61-96%). Most eyes (85%; 95% CI: 70-95%) gained clinically significant improvement in anterior chamber inflammation. One patient developed a colon perforation during treatment. No other major complications were recorded. Conclusions: Treatment of ocular inflammation with high-dose intravenous corticosteroids resulted in substantial clinical improvement for most cases within 1 month. Complications of therapy were infrequent. [ABSTRACT FROM AUTHOR]

Objectives. One of the neurobiological core features of schizophrenic illnesses is a hypo-functionality of the frontal cortex ('cerebral hypofrontality'). The two major classes of antipsychotic medication differ regarding their impact on frontal lobe function and metabolism, with a presumably more positive effect of 'atypical' compared to 'typical' agents. To date, neurobiological markers reliably predicting the treatment response to different antipsychotics are lacking. The present study, therefore, aimed at establishing a neurophysiological marker of frontal lobe function (NoGo-Anteriorization, NGA) as a predictor of the treatment response to first- and second-generation antipsychotics. Methods. Seventy-six schizophrenic patients were examined three times over a 6-week study period. Patients were treated with first- or second-generation antipsychotics, and NGA, neurocognitive performance, and symptomatology were assessed on admission as well as during two follow-up measurements. Results. Baseline NGA values significantly predicted the treatment response to typical and atypical antipsychotics; however, the direction of this prediction was dependent on the antipsychotic drug regimen. Moreover, atypical antipsychotics had a superior impact on neurocognitive performance and self-reported quality of life. Conclusions. The NGA might be a useful tool in developing individualized treatment strategies based on pathophysiological aspects of schizophrenic illnesses that can be easily determined in clinical routine settings. [ABSTRACT FROM AUTHOR]

In this article the authors reflect on regulations which have been developed to protect research subjects and data in research which uses human subjects. They suggest that regulations related to informed consent and privacy protection are burdensome in research which uses human subjects. They argue that a new category of research risk must be established which informs research subjects of the level of risk that they will be exposed to by participating in the research.

Abstract: This paper applies concepts from the sociology and anthropology of organizations to understand limits to the implementation of a more effective safety culture in the workplace. It highlights unintended consequences of combining bureaucratic control and shared governance and identifies sources of inertia within already existing safety cultures. The data come from focus group interviews with workers in a research and development facility of a multinational corporation in the Western U.S. It is found that safety protocols, rules, and rhetoric, combined with efforts to give workers more responsibility for safety in the workplace, create tendencies toward worker alienation, shame with regard to injuries, complacency, and fear of bureaucratic processes. Therefore it appears that some efforts to create safety culture in the workplace may unintentionally undermine the goal of manufacturing safety. [Copyright &y& Elsevier]

Panic disorder still remains a pervasive, life quality impairing disorder requiring adequate treatment options. In this case report we present the data of a patient with panic disorder and comorbid depression who was treated with high-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the left prefrontal cortex over a course of 3 weeks. Measurements of the cerebral oxygenation with near-infrared spectroscopy (NIRS) during an emotional Stroop task before and after the rTMS treatment suggests that rTMS may modulate panic-related prefrontal brain dysfunctions in panic patients and that it may serve as a possible treatment option for anxiety disorders. [ABSTRACT FROM AUTHOR]

Purpose: To describe cytomegalovirus (CMV) end-organ disease (EOD) rate in AIDS patients with low CD4+ cell count despite HAART who were enrolled in a randomized, placebo-controlled trial of preemptive valganciclovir (VGCV) to prevent CMV EOD in those with CMV viremia. Methods: Subjects (N = 338) were HIV-infected with CD4+ count 3, plasma HIV RNA >400 copies/mL, and on stable or no HAART. All underwent plasma CMV DNA PCR testing every 8 weeks (Step 1); those with detectable CMV DNA were randomized to VGCV or placebo (Step 2). Results: Plasma CMV DNA was detected in 68 (20%), of whom 4 developed CMV EOD. During Step 1, 53 died. Of the 47 who entered Step 2 (24 VGCV, 23 placebo), CMV EOD was diagnosed in 10 (4 VGCV, 6 placebo) and 15 died (7 VGCV, 8 placebo). Of those randomized to placebo, 14% were diagnosed with CMV EOD at 12 months. Conclusions: We observed a lower CMV EOD rate among subjects receiving HAART than predicted based on published literature. However, mortality was high in this study. Our findings suggest that preemptive anti-CMV therapy in patients with persistently low CD4+ cell counts in the current treatment era may not be warranted given the low incidence of CMV EOD and high all-cause mortality observed in this study population. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate potential epidemiologic methods for studying long-term effects of immunosuppression on the risk of mortality and fatal malignancy, and present the methodological details of the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study. Methods: Advantages and disadvantages of potential study designs for evaluating rare, late-occurring events are reviewed, and the SITE Cohort Study approach is presented. Results: The randomized, controlled trial is the most robust method for evaluating treatment effects, but long study duration, high costs, and ethical concerns when studying toxicity limit its use in this setting. Retrospective cohort studies are potentially more cost-effective and timely, if records exist providing the desired information over sufficient follow-up time in the past. Case-control methods require extremely large sample sizes to evaluate risk associated with rare exposures, and recall bias is problematic when studying mortality. The SITE Cohort Study is a retrospective cohort study. Past use of antimetabolites, T-cell inhibitors, alkylating agents, and other immunosuppressives is ascertained from medical records of ∼ 9,250 ocular inflammation patients at five tertiary centers over up to 30 years. Mortality and cause-specific mortality outcomes over ∼ 100,000 person-years are ascertained using the National Death Index. Immunosuppressed and non-immunosuppressed groups of patients are compared with each other and general population mortality rates from US vital statistics. Calculated detectable differences for mortality/fatal malignancy with respect to the general population are 22%/49% for antimetabolites, 28%/62% for T-cell inhibitors, and 36%/81% for alkylating agents. Conclusions: Information from the SITE Cohort Study should clarify whether use of these immunosuppressive drugs for ocular inflammation increases the risk of mortality and fatal cancer. This epidemiologic approach may be useful for evaluating long-term risks of systemic therapies for other ocular diseases. [ABSTRACT FROM AUTHOR]

Anecdotal data have suggested that retention of HIV-infected patients with immune recovery in longitudinal studies may be difficult as they resume normal activities. This study evaluated risk factors for attrition among patients with AIDS in a cohort study in the era of highly active antiretroviral therapy. Patients with AIDS enrolled in the Longitudinal Study of Ocular Complications of AIDS were evaluated every three months with demographic, clinical and laboratory data collected. Lost to follow-up was defined as any patient who missed all study visits and could not be contacted for 12 consecutive months, who had not died and who did not re-enter the study at a later date. Of the 1,052 patients studied, 77 (7.3%) were lost to follow-up (rate = 0.03/person year). In the multivariate analysis, factors associated with attrition were CD4+ T-cell count category (hazard ratio (HR) = 2.03; 95%CI: 1.01, 4.24; P =0.05 for CD4+ count ≤ 50 cells/µL and HR = 1.96; 95%CI: 1.12, 3.40; P =0.02 for CD4+ count 51–200 cells/µL) and detectable HIV viral load (HR = 1.29; 95%CI: 1.07, 1.53; P 400 copies/mL). These data suggest that patients with compromised immunologic status are at an increased risk for being lost to follow-up. [ABSTRACT FROM AUTHOR]

P2X receptor function in the CNS is poorly understood, and currently available data are partly inconsistent. In the presented study, we investigated P2X 3 receptors stably expressed in HEK293 cells. Non-stationary noise analysis of whole cell currents and rapid ATP application through flash photolysis allowed for assessing the single channel conductance (6.6&ThickSpace;pS) and the fast activation kinetics of the receptor (20&ThickSpace;ms). The characteristics of channel desensitization and pharmacological properties matched previous findings. The properties of wild type receptors were compared with P2X 3 constructs carrying a fluorescent tag (ECFP or DsRed 2 ) at the C-terminus. These fluorescently labeled subunits formed functional receptors, with neither the affinity of the ligand binding site nor channel properties (ion selectivity, gating kinetics, single channel conductance) differing from wild type. We conclude that both fusion proteins tested here are suitable for generating transgenic mice, which can be expected to promote understanding of the physiological role of P2X 3 receptors in CNS signaling. [ABSTRACT FROM AUTHOR]

Purpose: To describe a keratopathy in patients with the human immunodeficiency virus (HIV) infection. Methods: Retrospective review of ophthalmic and medical records, including laboratory evaluations, of seven patients with HIV infection and posterior intracorneal opacities. Results:Each patient had a bilateral peripheral keratopathy located at the level of the Descemet membrane that was unassociated with intraocular inflammation. All patients were receiving highly active antiretroviral therapy (HAART). All patients had elevations in their CD4+ T-lymphocyte counts due to HAART prior to presenting with the corneal opacities. Five of the seven patients had elevated serum cholesterol, triglycerides, or both. Best-corrected visual acuity was 20/25 or better in six of the seven patients at the time of diagnosis, and vision remained stable through the follow-up period in all patients (median follow-up: 25 months; range: 14–82 months). The corneal opacities remained unchanged in all seven over the follow-up period. Conclusion:These patients have a bilateral keratopathy that appears to be non-progressive and has no effect on visual acuity. [ABSTRACT FROM AUTHOR]

This article presents information on treatment of ocular inflammation. Ocular inflammatory disorders, such as uveitis and scleritis, are severe ocular problems with high rates of visual loss. Treatments for ocular inflammation include corticosteroids, oral nonsteroidal anti-inflammatory drugs for anterior scleritis, and immunosuppressive drugs. Clinical experience with corticosteroid therapy for ocular inflammation has resulted in the following guidelines for their use. Topical corticosteroids typically are appropriate for anterior uveitis and mild forms of ocular surface disease.

Vegetarians exclude various forms of animal‐derived foods from consumption, and consequently must use special strategies to make food choices and present their food decisions to others. This study investigated the ways people following vegetarian diets managed their food choices and negotiated their interactions with others. Qualitative methods were used to interview 19 self‐identified vegetarians recruited by snowball sampling. Many respondents followed vegan diets, but the majority consumed some form of animal foods. The vegetarians in this sample self‐consciously labeled themselves ‘Vegetarians,” and adopted and used a vegetarian identity that included normative behavioral expectations. To manage social interactions, vegetarians sometimes ate animal‐derived foods not in their usual diets in particular situations and used explanations in the form of accounts and discounting in constructing justifications for those behaviors. Understanding management of vegetarianism as a process reveals barriers and enabling factors for dietary practices that differ from those of the predominant society. [ABSTRACT FROM PUBLISHER]

PurposeMethodsResultsConclusionChronic anterior uveitis (CAU) often requires suppressive therapy, which has potential side effects including cataract, ocular hypertension, and increased risk of infection. No remittive therapy is currently available; however, several studies have demonstrated an association between low 25-hydroxy Vitamin D (25OHD) levels and either uveitis incidence or uveitis disease activity. This study investigates the potential of Vitamin D supplementation as a remittive treatment for CAU.We conducted a retrospective analysis using data from the Systemic Immunosuppressive Therapy for Eye Disease (SITE) cohort study, which included patients with ocular inflammatory disease seen at U.S. tertiary centers between 1979 and 2010. Vitamin D supplementation data was analyzed for patients with CAU. Eyes were considered in remission if they remained quiet for at least 90 days off all anti-inflammatory treatment for eye disease.Among 2688 patients who never used Vitamin D, the cumulative adjusted CAU remission incidence was 13.5% at the 16-month follow-up. In contrast, among 75 patients who used Vitamin D for a duration of ≤1 year, the cumulative adjusted CAU remission incidence was 28% at 16 months. The use of Vitamin D was associated with a crude hazard ratio for remission of 2.14 [95% confidence interval (CI) 1.23–3.71, p = 0.0071], and an adjusted hazard ratio for remission of 2.43 [95% CI: 1.36–4.33, p = 0.0027].In the SITE Cohort, Vitamin D supplementation is associated with a significantly increased incidence of remission. Vitamin D supplementation should be explored in a prospective trial as the next step of evaluation. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionThe survey aims to explore the use of existing nomenclature and current clinical and multimodal imaging (MMI) approach in diagnosing white dot syndromes (WDS) among uveitis and retina specialists.The members of the International Uveitis Study Group (IUSG) task force MUV (Multimodal imaging in UVeitis) developed a survey. The questionnaire, created using Qualtrics, consisted of 22 questions. The responses were compared against regions, workplace setting, sub-specialty, and experience of the participants.A total of 432 participants initiated the background section; 343 initiated the investigation section and 263/343 completed the survey (76.7%). The majority (43.7%) reported a specialty/practice focus mostly on uveitis, 32.2% on uveitis and retina, and 20.1% mostly on retina. Specifically, 55.7% were in practice > 10 years post-fellowship and 65.8% worked in academic settings. The term WDS was not universally used in clinical practice, with no significant differences by region, subspecialty, experience, workplace setting or number of WDS patients managed in the prior year (p > 0.01). Nearly 90% of participants reported using MMI to diagnose WDS. More than 70% advocated redefining the nomenclature and classification of WDS based on the primary anatomical location of disease using MMI without significant regional or professional differences (p > 0.01).These results underscore the widespread adoption of MMI among uveitis and retina specialists in the characterization of entities traditionally grouped under the term WDS. Respondents strongly agree that MMI provides a precise distinction between these posterior uveitis, advocating for the overcoming of the clinical term WDS in favor of a patho-anatomic redefinition. [ABSTRACT FROM AUTHOR]

An experimentally determined rs -type structure of HNCNH is reported: rNH = 1.0074 A, rCN = 1.2242 A, /HNC = 118.63, /NCN = 170.63, /HN NH = 88.99 . The number of digits quoted allow for errors with two significant figures. In order to obtain these values we recorded rotational-torsional spectra of HN13CNH, H15NC15NH and DNCND, by using isotopically enriched cyanamide. A chemical equilibrium exists between carbodiimide, HNCNH, and the more stable isomer cyanamide, H2NCN, which strongly favours cyanamide (approximately 1:115 at 110 oC). The expensive C- and N-substituted isotopomers could only be investigated in the millimetre wave region, while for DNCND the far infrared spectrum between 10-350 cm-1 was also recorded. Rotational constants of the three isotopomers, as well as of the parent species, were determined by fitting the assigned spectral transitions to the Watson Hamiltonian in S reduction. Using fitting programs written by Schwendeman and Rudolph, r0, rs and rrho m structures of HNCNH were derived. The experimentally determined structural parameters are compared with an ab initio re structure. [ABSTRACT FROM AUTHOR]

Determines the prevalence and incidence of drug resistant cytomegalovirus (CMV) retinitis. Details on the baseline eye examination of patients prior to initiation of treatment; Risk factors for the development of resistant CMV; Correlation between clinical outcome as measured both by eye examination and fundus photography.

The redirection of T cell activity using bispecific antibodies is one of the most promising cancer immunotherapy approaches currently in development, but it is limited by cytokine storm-related toxicities, as well as the pharmacokinetics and tumor-penetrating capabilities of current bispecific antibody formats. Here, we have engineered the ATTACK (Asymmetric Tandem Trimerbody for T cell Activation and Cancer Killing), a novel T cell-recruiting bispecific antibody which combines three EGFR-binding single-domain antibodies (VHH; clone EgA1) with a single CD3-binding single-chain variable fragment (scFv; clone OKT3) in an intermediate molecular weight package. The two specificities are oriented in opposite directions in order to simultaneously engage cancer cells and T cell effectors, and thereby promote immunological synapse formation. EgA1 ATTACK was expressed as a homogenous, non-aggregating, soluble protein by mammalian cells and demonstrated an enhanced binding to EGFR, but not CD3, when compared to the previously characterized tandem bispecific antibody which has one EgA1 VHHand one OKT3 scFv per molecule. EgA1 ATTACK induced synapse formation and early signaling pathways downstream of TCR engagement at lower concentrations than the tandem VHH-scFv bispecific antibody. Furthermore, it demonstrated extremely potent, dose-dependent cytotoxicity when retargeting human T cells towards EGFR-expressing cells, with an efficacy over 15-fold higher than that of the tandem VHH-scFv bispecific antibody. These results suggest that the ATTACK is an ideal format for the development of the next-generation of T cell-redirecting bispecific antibodies. [ABSTRACT FROM PUBLISHER]

A letter to the editor about the role of both teachers and students in the academic success of students.

Purpose: To describe restoration of retinal architecture following systemic immunosuppressive treatment in a patient with birdshot chorioretinopathy (BSCR). Design: Case report. Methods: A patient with BSCR and vitritis, reduced electroretinographic responses, and a constricted visual field was treated with prednisone and mycophenolate mofetil. Results: Spectral domain optical coherence tomography (SD-OCT) at baseline demonstrated a disruption of retinal architecture. After 4 months of treatment retinal architecture, as visualized on SD-OCT, was restored to normal. Conclusions: Treatment of BSCR with systemic immunosuppression can result in restoration of disrupted retinal architecture. This structural improvement can be visualized and assessed using SD-OCT. [ABSTRACT FROM AUTHOR]

The article discusses the epidemiology of uveitis. Although considered to be an uncommon disease, uveitis is said to be the fifth or sixth leading cause of blindness in the U.S. It is said to be characterized by intraocular inflammation, and is associated with other complications including cataract, glaucoma and nuclear edema. An overview of a study on the demographic and clinical features of uveitis is offered.

Purpose : To describe the occurrence of nodular scleritis in a patient developing tubulointerstitial nephritis and uveitis (TINU) syndrome. Design : Observational case report. Method : The case notes of a 57-year-old female presenting with recurrent nodular scleritis, who later developed interstitial nephritis with bilateral uveitis, were reviewed. Results : Common and established causes of scleritis were not present in an adult who developed the TINU syndrome a decade later. Conclusions : Although scleritis has not been reported as a tubulointerstitial nephritis-associated ocular inflammation, it may be part of the possible spectrum of ocular inflammation occurring as part of the TINU syndrome. [ABSTRACT FROM AUTHOR]