Effect of Virtual Reality on Stress Reduction and Change of Physiological Parameters Including Heart Rate Variability in People With High Stress: An Open Randomized Crossover Trial.

Introduction: Although, attempts to apply virtual reality (VR) in mental healthcare are rapidly increasing, it is still unclear whether VR relaxation can reduce stress more than conventional biofeedback. Methods: Participants consisted of 83 healthy adult volunteers with high stress, which was defined as a score of 20 or more on the Perceived Stress Scale-10 (PSS-10). This study used an open, randomized, crossover design with baseline, stress, and relaxation phases. During the stress phase, participants experienced an intentionally generated shaking VR and serial-7 subtraction. For the relaxation phase, participants underwent a randomly assigned relaxation session on day 1 among VR relaxation and biofeedack, and the other type of relaxation session was applied on day 2. We compared the State-Trait Anxiety Inventory-X1 (STAI-X1), STAI-X2, the Numeric Rating Scale (NRS), and physiological parameters including heart rate variability (HRV) indexes in the stress and relaxation phases. Results: A total of 74 participants were included in the analyses. The median age of participants was 39 years, STAI-X1 was 47.27 (SD = 9.92), and NRS was 55.51 (SD = 24.48) at baseline. VR and biofeedback significantly decreased STAI-X1 and NRS from the stress phase to the relaxation phase, while the difference of effect between VR and biofeedback was not significant. However, there was a significant difference in electromyography, LF/HF ratio, LF total, and NN50 between VR relaxation and biofeedback. Conclusion: VR relaxation was effective in reducing subjectively reported stress in individuals with high stress.

Clinical predictors of cybersickness in virtual reality (VR) among highly stressed people.

The use of virtual reality (VR) in the treatment of psychiatric disorders is increasing, and cybersickness has emerged as an important obstacle to overcome. However, the clinical factors affecting cybersickness are still not well understood. In this study, we investigated clinical predictors and adaptation effect of cybersickness during VR application in highly stressed people. Eighty-three healthy adult participants with high stress level were recruited. At baseline, we conducted psychiatric, ophthalmologic, and otologic evaluations and extracted physiological parameters. We divided the participants into two groups according to the order of exposure to VR videos with different degrees of shaking and repetitively administered the Simulator Sickness Questionnaire (SSQ) and the Fast Motion sickness Scale (FMS). There was no significant difference in changes in the SSQ or the FMS between groups. The 40-59 years age group showed a greater increase in FMS compared to the 19-39 years age group. Smoking was negatively associated with cybersickness, and a high Positive Affect and Negative Affect Schedule score was positively associated with cybersickness. In conclusion, changing the intensity of shaking in VR did not affect cybersickness. While smoking was a protective factor, more expression of affect was a risk factor for cybersickness.

Genetic relationships between the RACK1 homolog cpc-2 and heterotrimeric G protein subunit genes in Neurospora crassa.

Receptor for Activated C Kinase-1 (RACK1) is a multifunctional eukaryotic scaffolding protein with a seven WD repeat structure. Among their many cellular roles, RACK1 homologs have been shown to serve as alternative Gß subunits during heterotrimeric G protein signaling in many systems. We investigated genetic interactions between the RACK1 homolog cpc-2, the previously characterized Gß subunit gnb-1 and other G protein signaling components in the multicellular filamentous fungus Neurospora crassa. Results from cell fractionation studies and from fluorescent microscopy of a strain expressing a CPC-2-GFP fusion protein revealed that CPC-2 is a cytoplasmic protein. Genetic epistasis experiments between cpc-2, the three Gα genes (gna-1, gna-2 and gna-3) and gnb-1 demonstrated that cpc-2 is epistatic to gna-2 with regards to basal hyphae growth rate and aerial hyphae height, while deletion of cpc-2 mitigates the increased macroconidiation on solid medium observed in Δgnb-1 mutants. Δcpc-2 mutants inappropriately produce conidiophores during growth in submerged culture and mutational activation of gna-3 alleviates this defect. Δcpc-2 mutants are female-sterile and fertility could not be restored by mutational activation of any of the three Gα genes. With the exception of macroconidiation on solid medium, double mutants lacking cpc-2 and gnb-1 exhibited more severe defects for all phenotypic traits, supporting a largely synergistic relationship between GNB-1 and CPC-2 in N. crassa.

Correlation and Agreement Between Cirrus HD-OCT "RNFL Thickness Map" and Scan Circle Retinal Nerve Fiber Layer Thickness Measurements.

PURPOSE: To evaluate the correlation and agreement between optical coherence tomography (Cirrus HD-OCT) retinal nerve fiber layer (RNFL) thickness map and scan circle RNFL thickness measurements. METHODS: ImageJ and custom Perl scripts were used to derive RNFL thickness measurements from RNFL thickness maps of optic disc scans of healthy and glaucomatous eyes. Average, quadrant, and clock-hour RNFL thickness of the map, and RNFL thickness of the areas inside/outside the scan circle were obtained. Correlation and agreement between RNFL thickness map and scan circle RNFL thickness measurements were evaluated using R and Bland-Altman plots, respectively. RESULTS: A total of 104 scans from 26 healthy eyes and 120 scans from 30 glaucomatous eyes were analyzed. RNFL thickness map and scan circle measurements were highly reproducible (eg, in healthy eyes, average RNFL thickness coefficients of variation were 2.14% and 2.52% for RNFL thickness map and scan circle, respectively) and highly correlated (0.55 ≤ R ≤ 0.98). In general, the scan circle provided greater RNFL thickness than the RNFL thickness map in corresponding sectors and the differences tended to increase as RNFL thickness increased. The width of the 95% limits of agreement ranged between 5.28 and 36.80 µm in healthy eyes, and between 11.69 and 42.89 µm in glaucomatous eyes. CONCLUSIONS: Despite good correlation between RNFL thickness map and scan circle measurements, agreement was generally poor, suggesting that RNFL thickness assessment over the entire scan area may provide additional clinically relevant information to the conventional scan circle analysis. In the absence of available measurements from the entire peripapillary region, the RNFL thickness maps can be used to investigate localized RNFL thinning in areas not intercepted by the scan circle.

Outflow tract ablation using a conditionally cytotoxic feline immunodeficiency viral vector.

PURPOSE: To create an in vivo model of vector-mediated trabecular meshwork (TM) ablation and replacement. METHODS: We generated a conditionally cytotoxic, trackable vector, HSVtkiG, that expressed herpes simplex virus 1 thymidine kinase (HSVtk) and enhanced green fluorescent protein (eGFP). We optimized HSVtkiG ablation in vitro with ganciclovir (GCV) in comparison to eGFP control vector GINSIN and investigated the mechanism. Right eyes of 24 rats were then injected intracamerally with either HSVtkiG or GINSIN, before intraperitoneal GCV was administered 1 week later. Intraocular pressure, central corneal thickness (CCT), and slit-lamp exams were assessed for 8 weeks. Transduction and ablation were followed by gonioscopic visualization of eGFP. Histology was obtained with TM cell counts and immunohistochemistry markers of inflammation. RESULTS: Transduction and ablation parameters were established in vitro. Apoptosis was the cause of cell death. In vivo, transduction was seen gonioscopically to be targeted to the TM, followed by disappearance of eGFP marker fluorescence in HSVtkiG-transduced cells after injection of GCV. Ablation resulted in an IOP decrease of 25% in HSVtkiG-injected eyes 2 days after GCV but not in GINSIN or noninjected control eyes (P < 0.05). Trabecular meshwork cellularity was decreased at the time of lowest IOP and recovered thereafter, while CCT remained unchanged. Inflammation was absent. CONCLUSIONS: A vector-based system for inducible ablation of cells of the outflow tract was developed. Trabecular meshwork ablation lowered IOP, and recovery of cellularity and IOP followed. This model may be useful to study pressure regulation by the TM, its stem cells, and migration patterns.

Cup-to-Disc Ratio in Idiopathic Intracranial Hypertension without Papilloedema.

This study seeks to characterise potential differences in the cup-to-disc ratio (CDR) of patients with idiopathic intracranial hypertension (IIH) with papilloedema (IIHWP) compared with IIH without papilloedema (IIHWOP). The medical charts, optical coherence tomography (OCT), and digital optic disc photos of 30 patients (59 eyes) with IIHWP and 4 patients (8 eyes) with IIHWOP were reviewed retrospectively. The CDR values of the two groups were analysed using the Wilcoxon-Mann-Whitney test. Results showed a statistically significant smaller CDR in patients with IIHWP as compared with IIHWOP. These findings suggest that structural factors of the optic disc may play a role in the development of or lack thereof of papilloedema in patients with IIH.

Post-traumatic amaurosis secondary to paraophthalmic internal carotid artery pseudoaneurysm treated with pipeline embolization device.

During evaluation for monocular visual loss, a 48-year-old woman was found to have a posttraumatic paraophthalmic internal carotid artery (ICA) pseudoaneurysm. She underwent reconstruction of the ophthalmic segment of the right ICA with a Pipeline embolization device but her vision did not return.

Effect of symptom duration on outcomes following vitrectomy repair of primary macula-off retinal detachments.

PURPOSE: To examine the effect of symptom duration on visual and anatomical outcomes following pars plana vitrectomy repair of primary macula-off rhegmatogenous retinal detachments. METHODS: This is a retrospective, consecutive, interventional case series. All eyes underwent repair of macula-off rhegmatogenous retinal detachment with a 20-gauge, 23-gauge, or 25-gauge standard 3-port pars plana vitrectomy. Eyes with previous retinal surgery, giant retinal tear, Grade C or higher proliferative vitreoretinopathy, or less than 6 months of follow-up were excluded from the study. The main outcome measure studied was final best-corrected visual acuity (BCVA) as dependent on the duration of macular detachment symptoms. The secondary outcomes studied were single surgery anatomical success and complication rates. Visual acuity analysis was performed on all eyes that were pseudophakic by the final follow-up visit. RESULTS: Overall, 81 eyes of 81 patients met inclusion criteria, with a mean follow-up length of 55 months (range, 6-171 months) and mean duration of macular detachment symptom of 12 days (range, 1-64 days). The mean final BCVA was 20/40 (range, 20/20 to hand motion), with 70% (n = 57) of all patients obtaining 20/40 or better final BCVA. Patients with symptom duration of 6 days or less achieved better final BCVA (mean 20/25, n = 34) than patients with longer symptom duration (mean 20/50, n = 47) (t-test, P = 0.0030; α = 0.005). After 7 days of macular detachment, no significant difference was seen in final BCVA (t-test, P > 0.05). The overall single surgery anatomical success rate was 88% (71 of 81 eyes). There was no correlation between the single surgery anatomical success rate and duration of macular detachment symptom (Fisher's exact test, P > 0.10). CONCLUSION: Primary pars plana vitrectomy repair results in good final visual outcome for patients with primary macula-off rhegmatogenous retinal detachments. Surgical repair within 6 days of the symptom onset yielded better visual outcomes. After 7 days, visual outcome was not affected by the timing of the surgical repair. Anatomical outcome following pars plana vitrectomy repair is not affected by symptom duration.

Down but not out.

A 20-year-old Hispanic man with Down syndrome presented with progressively worsening headache, fluctuating decreased vision, and bilateral optic disk edema. Magnetic resonance imaging of the head showed an empty sella, and magnetic resonance venography showed thrombosis of left transverse and sigmoid sinuses. Catheter angiography angiogram showed a dural arteriovenous fistula in the wall of left transverse and sigmoid sinuses. The patient underwent Onyx endovascular embolization of the fistula, resulting in its angiographic obliteration, followed by resolution of his clinical signs and symptoms.

Conjugal giant cell arteritis.

While the pathogenesis of giant cell arteritis (GCA) remains unclear, a number of factors may be contributory, including genetic, environmental, and immune. There have been few reports of GCA occurring in a conjugal pair, all originating from Northern Europe or the Northern United States. We document GCA occurring in a husband and wife from the southern Gulf Coast of the United States and discuss the implications of this, as well as the current understanding of the pathogenesis of GCA.

Rhino-orbital Mucormycosis Treated Successfully with Posaconazole without Exenteration.

Mucormycosis is a rare and often fatal opportunistic angioinvasive infection seen mostly in immunocompromised patients, such as those with diabetes mellitus, cancer, or renal failure. Ophthalmic manifestations of orbital mucormycosis include ocular pain, periocular oedema, visual loss, ophthalmoplegia, proptosis, and ptosis. Although therapy for orbital mucormycosis consists of maximally tolerated doses of antifungal agents (e.g., amphotericin B) and extensive surgical debridement, treatment remains ineffective in up to 20% of cases. We describe two patients with rhino-orbitalmucormycosis who were successfully treated with posaconazole in conjunction with intravenous (IV) amphotericin B and sinus surgical debridement. These cases highlight several unusual early manifestations of orbital mucormycosis, including disc oedema and amaurosis fugax, as well as the applicability of a new extended-spectrum antifungal agent in management of orbital zygomycosis.

Neuroimaging in ophthalmology.

In the past three decades, there have been countless advances in imaging modalities that have revolutionized evaluation, management, and treatment of neuro-ophthalmic disorders. Non-invasive approaches for early detection and monitoring of treatments have decreased morbidity and mortality. Understanding of basic methods of imaging techniques and choice of imaging modalities in cases encountered in neuro-ophthalmology clinic is critical for proper evaluation of patients. Two main imaging modalities that are often used are computed tomography (CT) and magnetic resonance imaging (MRI). However, variations of these modalities and appropriate location of imaging must be considered in each clinical scenario. In this article, we review and summarize the best neuroimaging studies for specific neuro-ophthalmic indications and the diagnostic radiographic findings for important clinical entities.

Use of 1H nuclear magnetic resonance to measure intracellular metabolite levels during growth and asexual sporulation in Neurospora crassa.

Conidiation is an asexual sporulation pathway that is a response to adverse conditions and is the main mode of dispersal utilized by filamentous fungal pathogens for reestablishment in a more favorable environment. Heterotrimeric G proteins (consisting of α, ß, and γ subunits) have been shown to regulate conidiation in diverse fungi. Previous work has demonstrated that all three of the Gα subunits in the filamentous fungus Neurospora crassa affect the accumulation of mass on poor carbon sources and that loss of gna-3 leads to the most dramatic effects on conidiation. In this study, we used (1)H nuclear magnetic resonance (NMR) to profile the metabolome of N. crassa in extracts isolated from vegetative hyphae and conidia from cultures grown under conditions of high or low sucrose. We compared wild-type and Δgna-3 strains to determine whether lack of gna-3 causes a significant difference in the global metabolite profile. The results demonstrate that the global metabolome of wild-type hyphae is influenced by carbon availability. The metabolome of the Δgna-3 strain cultured on both high and low sucrose is similar to that of the wild type grown on high sucrose, suggesting an overall defect in nutrient sensing in the mutant. However, analysis of individual metabolites revealed differences in wild-type and Δgna-3 strains cultured under conditions of low and high sucrose.

From the Cover: Whole-genome association study identifies STK39 as a hypertension susceptibility gene.

Hypertension places a major burden on individual and public health, but the genetic basis of this complex disorder is poorly understood. We conducted a genome-wide association study of systolic and diastolic blood pressure (SBP and DBP) in Amish subjects and found strong association signals with common variants in a serine/threonine kinase gene, STK39. We confirmed this association in an independent Amish and 4 non-Amish Caucasian samples including the Diabetes Genetics Initiative, Framingham Heart Study, GenNet, and Hutterites (meta-analysis combining all studies: n = 7,125, P < 10(-6)). The higher BP-associated alleles have frequencies > 0.09 and were associated with increases of 3.3/1.3 mm Hg in SBP/DBP, respectively, in the Amish subjects and with smaller but consistent effects across the non-Amish studies. Cell-based functional studies showed that STK39 interacts with WNK kinases and cation-chloride cotransporters, mutations in which cause monogenic forms of BP dysregulation. We demonstrate that in vivo, STK39 is expressed in the distal nephron, where it may interact with these proteins. Although none of the associated SNPs alter protein structure, we identified and experimentally confirmed a highly conserved intronic element with allele-specific in vitro transcription activity as a functional candidate for this association. Thus, variants in STK39 may influence BP by increasing STK39 expression and consequently altering renal Na(+) excretion, thus unifying rare and common BP-regulating alleles in the same physiological pathway.

Inhibition of infectious human immunodeficiency virus type 1 virions via lentiviral vector encoded short antisense RNAs.

During the life cycles of most retroviruses and lentiviruses, dimerization and packaging of two copies of viral genomic RNA is required for the subsequent conversion of RNA into double stranded DNA by reverse transcriptase. For human immunodeficiency virus type 1 (HIV-1), dimerization is mediated by interactions of the stem-loop structures in the dimerization-packaging, or psi (Psi) domain. We have tethered anti-HIV gag ribozymes and small antisense RNAs to the HIV Psi domain in an HIV-1 lentiviral vector to facilitate copackaging of these replication inhibitors with HIV genomic RNAs during HIV infectious challenge. In order to maximize the base pairing of the ribozymes or antisense segments to the HIV-1 genomic target, sequences in HIV-1 were identified that are highly accessible to antisense pairing. Ribozymes or antisense RNAs designed to target these sequences were inserted in the lentiviral vector at the same relative distance to the Psi element as the HIV-1 target sites. Packaged vectors were transduced into CEM cells followed by challenges with HIV-1. Only the constructs that harbored short antisense segments complementary to HIV-1 gag produced replication incompetent HIV-1. These results demonstrate that a short stretch of antisense pairing downstream of the dimerization domain in an HIV-based vector can drive dimerization and provide a powerful approach for inhibition of HIV-1.

Negative feedback inhibition of HIV-1 by TAT-inducible expression of siRNA.

Here we demonstrate that an inducible anti-HIV short hairpin RNA (shRNA) expressed from a Pol II promoter inhibits HIV-1 gene expression in mammalian cells. Our strategy is based on a promoter system in which the HIV-1 LTR is fused to the Drosophila hsp70 minimal heat shock promoter. This system is inducible by HIV-1 TAT, which functions in a negative feedback loop to activate transcription of an shRNA directed against HIV-1 rev. Upon induction the shRNA is processed to an siRNA that guides inhibition of HIV replication in cultured T-lymphocytes and hematopoietic stem cell-derived monocytes. The fusion promoter system may be safer than drug-inducible systems for shRNA-mediated gene therapy against HIV as the shRNAs are only expressed following HIV infection.