Analysis of retinal and choroidal microvascular changes using optical coherence tomography and optical coherence tomography angiography in patients with acute leukemia.

PURPOSE: Although leukemic retinopathy accounts for 80% of ocular complications in acute leukemia, its pathogenesis remains unclear. To evaluate changes in retinal and choroicapillaris and structural parameters in patients with acute leukemia, we analyzed the correlation between vascular perfusion metrics and laboratory parameters and assessed the changes after hematopoietic stem cell transplantation (HSCT). METHODS: Herein, 104 eyes of 52 patients aged 18 and above with acute leukemia were enrolled. 80 eyes of 40 healthy patients were recruited as control participants. All participants underwent optical coherence tomography (OCT) and OCT angiography (OCTA) at baseline. RESULTS: Patients with acute leukemia had a significantly thicker ganglion cell-inner plexiform layer (GCIPL) and lower circularity index than the control participants. Post-HSCT perfusion metrics did not differ significantly, but parafoveal thickness decreased significantly. During the active phase of acute leukemia, lower platelet levels were associated with significant GCIPL thickening and increased foveal avascular zone and perimeter. D-dimer levels positively correlated with GCIPL thickness. CONCLUSION: Patients with acute leukemia had subclinical retinal microvascular deficits on OCTA and GCIPL thickening on OCT, possibly associated with bone marrow function. GCIPL thickness may indicate acute ischemia in such patients. Further studies must elucidate their clinical and prognostic significance.

Alteration of perivascular reflectivity on optical coherence tomography of branched retinal vein obstruction.

This study aimed to evaluate perivascular reflectivity in patients with branched retinal vascular obstruction (BRVO) using en-face optical coherence tomography (OCT). The study retrospectively analyzed 45 patients with recurrent BRVO, 30 with indolent BRVO, and 45 age- and sex-matched controls. Using a 3.0 × 3.0-mm deep capillary plexus slab on macular scans, OCT angiography (OCTA) and structural en-face OCT scans were divided into four quadrants. Obstructive quadrants of OCTA scans were binarized using a threshold value of mean + 2 standard deviation. The selected area of high signal strength (HSS) was applied to the structural en-face OCT scans, and the corrected mean perivascular reflectivity was calculated as the mean reflectivity on the HSS area/overall en-face OCT mean reflectivity. The same procedure was performed in the quadrants of the matched controls. Regression analysis was conducted on several factors possibly associated with corrected perivascular reflectivity. The perivascular reflectivity in the obstructive BRVO quadrant was significantly higher than in the indolent BRVO and control quadrants (P = 0.009, P = 0.003). Both univariate and multivariate regression analyses showed a significant correlation between the average number of intravitreal injections (anti-vascular endothelial growth factor or dexamethasone implant) per year and refractive errors and image binarization threshold and perivascular reflectivity (P = 0.011, 0.013, < 0.001/univariate; 0.007, 0.041, 0.005/multivariate, respectively). En-face OCT scans of the deep capillary plexus slab revealed higher perivascular reflectivity in recurrent BRVO eyes than in indolent BRVO and control eyes. The results also indicate a remarkable correlation between perivascular reflectivity and the average number of intravitreal injections, suggesting a link to recurrence rates.

En-face optical coherence tomography hyperreflective foci of choriocapillaris in central serous chorioretinopathy.

The purpose of this study is to evaluate choroidal hyperreflective foci (HRF) changes in central serous chorioretinopathy (CSC) on en-face optical coherence tomography (OCT). Retrospective analysis of 42 patients with unilateral CSC (84 eyes, including fellow eyes for controls) and 42 age- and sex-matched controls. With 4.5 × 4.5 mm macular scans, structural en-face OCT choriocapillaris (CC) slabs were used to calculate the density and number of HRF in acute CSC eyes with serous retinal detachment (SRD), resolved CSC eyes without SRD, unaffected fellow eyes, control eyes, and 1-year follow-up eyes. Based on the 2-disc diameter (3000 µm), the en-face OCT scan was divided into foveal and perifoveal lesion and analyzed to consider the impact of SRF in HRF measurement. Regression analyses were performed on the several factors with HRF number and density in the acute and resolved CSC eyes. The perifoveal density and number of CC HRF was significantly lower in the resolved CSC eyes when compared to the acute CSC eyes (P = 0.002, both), fellow eyes (P = 0.042/density, 0.028/number), and controls (P = 0.021/density, P = 0.003/number). There was no significant difference between the acute CSC eyes, fellow eyes, controls, and 1-year follow-up eyes. As subfoveal choroidal thickness decreased and choroidal vascularity (CVI) increased, the perifoveal density and number of HRF was measured higher with a significant correlation in univariate regression analysis of the acute and resolved CSC eyes (all, P < 0.05). The authors hypothesized that stromal edema induced by choroidal congestion and hyperpermeability has the greatest influence on HRF measurement, possibly affected by inflammatory cells and materials extravasation.

Serial choriocapillaris flow changes in eyes with branched retinal vascular obstruction (BRVO).

PURPOSE: To evaluate the choriocapillaris (CC) flow changes in branched retinal vascular obstruction (BRVO) on optical coherence tomography angiography (OCTA). METHODS: Retrospective analysis of 29 patients with unilateral BRVO (58 eyes, including unaffected fellow eyes for controls). 4.5 x 4.5 mm macular scans were divided into 4 quadrants. Serial analyses were conducted on CC flow voids of the opposite quadrant to the active occluded area in BRVO eyes. Each of the quadrants were also compared to the occluded quadrant of resolved eyes and the contralateral quadrant of fellow eyes by matched data analysis. A regression analysis was performed on the several parameters (Choroidal thickness; CT, Choroidal vascularity index; CVI, Central macular thickness; CMT, The number of intravitreal injections) and CC flow voids. RESULTS: The CC flow void increased sequentially: The uninvolved quadrant of acute BRVO-affected eyes, that of resolved eyes after 3-month/1-year, the contralateral quadrant of fellow eye, the involved (occluded) quadrant of resolved eyes. There were significant correlations between initial CMT, the number of injections and the CC flow void of uninvolved quadrants (P = 0.025, 0.031, respectively), and between the involved (occluded) quadrants and fellow CT (P = 0.029). CONCLUSION: CC flow void of uninvolved macular areas decreased significantly in eyes with acute BRVO, suggesting that CC changes were limited to the blocked area and a compensatory mechanism would work in surrounding areas.

Quantitative analysis of choroidal blood flow parameters in optical coherence tomography and angiography in central serous chorioretinopathy.

PURPOSE: To evaluate the choriocapillaris (CC) flow in central serous chorioretinopathy (CSC) and determine the relationship between CC flow void with the choroidal thickness (CT) and choroidal vascularity index (CVI). METHODS: Retrospective analysis of 20 patients with CSC (40 eyes, including unaffected fellow eyes) and 20 age- and sex-matched controls. After compensation with optical coherence tomography (OCT) en-face structural image, the CC flow void (%) was measured using the phansalkar threshold with a window radius of 3 and 15 pixels. The mean CC flow voids of acute CSC, recovered-acute CSC, unaffected fellow, and control eyes were compared by matched data analysis. A regression analysis was performed on the choroidal parameters (CT and CVI) and CC flow voids. RESULTS: The CC flow void had an increasing tendency in the following order: control, fellow, recovered-acute CSC, and acute CSC eyes. Acute/recovered comparison showed a significant P value (0.008) in the foveal lesion. Recovered/fellow and fellow/control presented significant P values regardless of location to fovea (all <0.05). There were significant positive correlations between CT and CC flow void (P < 0.05) in the acute CSC, recovered-acute CSC eyes. CONCLUSION: The CC flow on OCT angiography decreased in acute CSC eyes, especially in the foveal lesion, with a published compensation method. The findings suggest that unmodulated choroidal blood flow contributed to partially reversible diminished CC flow.

Changes in choroidal vascular structure from vitreoretinal lymphoma and the intraocular cytokine level associated with clinical resolution after intravitreal methotrexate treatment.

PURPOSE: To evaluate changes in choroidal vascular structure and aqueous cytokine levels in eyes with vitreoretinal lymphoma (VRL) after intravitreal methotrexate (MTX) treatment. METHODS: In this retrospective study, VRL patients who visited our hospital between October 2018 and July 2020 were reviewed. Aqueous samples were obtained before treatment and at clinical resolution after intravitreal MTX therapy. Interleukin (IL)-6 and IL-10 levels and the IL-10-to-IL-6 ratio were evaluated. Swept-source optical coherence tomographic images were obtained along with the aqueous samples. Subfoveal choroidal thickness (SFCT), total vascular area of the choroid (TCA), stromal area (SA), luminal area (LA), and choroidal vascularity index (CVI) were assessed. RESULTS: Twelve patients were enrolled (female:male-5:7). The mean age (± standard deviation) at diagnosis was 60.9±8.5 years. In the 16 eyes diagnosed with VRL, values of SFCT, TCA, LA, and SA significantly decreased after treatment (all p-values <0.05). Additionally, the aqueous cytokine IL-10 level and IL-10-to-IL-6 ratio were significantly decreased (p = 0.001 and p = 0.003, respectively). The choroidal structure in the non-treated fellow eyes did not show any significant difference. There were no further changes in SFCT, TCA, LA, or CVI that occurred during maintenance therapy. For clinical remission, the patients received 7.7±5.5 intravitreal MTX injections. The required number of injections for clinical remission was positively correlated with best-corrected visual acuity, IL-10, and IL-6 levels in the active phase (p = 0.035, p = 0.009, and p = 0.031, respectively). CONCLUSION: Eyes with active VRL exhibited choroidal thickening with increased vascular and stromal areas that decreased after remission following MTX treatment. Higher aqueous IL-10 and IL-6 levels and lower visual acuity in the active phase may indicate the number of injections required for remission; this should be considered in the treatment of patients with VRL.

Characteristics of retinal detachment associated with atopic dermatitis.

BACKGROUND: To examine the characteristics of rhegmatous retinal detachment (RRD) associated with atopic dermatitis. METHOD: Medical records of 2257 patients who underwent RD surgery at this clinic between 2008 and 2018 were retrospectively reviewed. Among them, 61 patients who were diagnosed as AD were assigned into the experimental group and 100 patients who did not have AD were randomly selected and assigned into the control group. Demographics, characteristics of detachment, initial operative method, and prognosis after surgery were investigated as main outcomes. Additionally, in pseudophakic RD patients, the period between the cataract surgery and onset of RD was measured. RESULT: Postoperative VA and prognosis were significantly worse and bilateral involvement of RD was more common in the atopy group than in the control group. (P value = 0.005, 0.001 each) Characteristics of retinal breaks were different between the two groups. Additionally, the risk of developing RD within 1 year after cataract surgery was significantly higher in pseudophakic patients of the atopic group than in the control group. (P value = 0.013) However, there was no significant difference in mean preoperative VA or refractive index between the two groups. CONCLUSION: Our results show that in atopic patients, RD occurs at a young age with different characteristics compared to non-atopic patients. Atopic RD has a poor visual prognosis. Thus, it requires careful management. Furthermore, the risk of developing RD within 1 year after cataract surgery is higher in atopic patients. Therefore, it is important to perform regular and extensive check-up after cataract surgery for atopic patients.

Clinical course after the onset of choroidal neovascularization in eyes with central serous chorioretinopathy.

ABSTRACT: Chronic central serous chorioretinopathy (CSC) can be complicated with choroidal neovascularization (CNV); however, the timing of its occurrence and its clinical significance are not well understood. This study aimed to observe the time of choroidal neovascularization detection after CSC diagnosis and determine whether clinical features and prognosis differed in patients with chronic CSC or age-related retinal degeneration.In this retrospective study, medical records of CSC patients complicated with CNV who visited Seoul St. Mary's hospital of Korea between October 2009 and December 2020 were reviewed. The presence of CNV was determined using fluorescein, indocyanine green, or optical coherent tomography angiography (OCTA). Based on the patients' medical records, we observed the change of clinical pattern, best-corrected visual acuity (BCVA) and central macular thickness (CMT) at CNV detection and at 6 months, 1 year, 3 years, and 5 years following CNV detection.Thirty eyes of 30 patients (male: female ratio of 13:17) were enrolled. Mean age at diagnosis of CSC was 54.0 ±â€Š8.5 years (mean ±â€Šstandard deviation). On average, CNV was detected 1.65 ±â€Š2.30 years after the diagnosis of CSC. The mean CMT was significantly decreased at 6 months, 1 year, and 3 years after choroidal neovascularization detection (P < .001, P < .001, P = .001 respectively). BCVA tend to improve after CNV detection, but there was no statistical significance at 6 months, 1 year, 3 years, and 5 years (all with P > .05). There were no clinical findings suggesting age-related macular degeneration such as intraretinal, subretinal hemorrhage or drusen in any of the case during follow-up. None of the subjects had severe visual acuity loss of 1.0 logarithm of the minimum angle of resolution (logMAR) (20/200 Snellen equivalent) or greater. Among the subjects, 6 patients (20%) did not require any treatment during observation, while 24 other patients required anti-vascular endothelial growth factor (anti-VEGF) or photodynamic therapy. At the last visit, 22 patients (73.3%) remained stable for more than 6 months, without subretinal fluid recurrence.Choroidal neovascularization was detected earlier than previously reported. There was no rapid deterioration of visual acuity or clinical features even after CNV detection.

Serial changes in the aqueous IL-10 level after intravitreal methotrexate injection as an indicator of primary vitreoretinal lymphoma recurrence.

Primary vitreoretinal lymphoma (PVRL) often masquerades as other uveitic diseases. We investigated the aqueous cytokine level changes and the effects of intraocular methotrexate (MTX) in patients with PVRL. In this retrospective consecutive case-series study, we reviewed the records of 14 consecutive patients with PVRL treated between 2018 and 2020. The concentrations of interleukin (IL)-2, IL-6, IL-10, IL-12, IL-17, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were determined at baseline and several time points after intravitreal MTX injections during follow-up. Markedly elevated IL-10 levels and a higher IL-10/IL-6 ratio were found in patients with PVRL. The aqueous levels of IL-10, IL-12, and TNF-α, and the IL-10/IL-6 ratio significantly decreased at 1 month after intravitreal MTX therapy onset compared with the baseline values (P = 0.001, 0.002, 0.001, and 0.001, respectively). The mean duration to normalized IL-10 levels was 1.17 ± 0.4 months. Where serially recorded IL-10 levels were available, regular intravitreal MTX treatment was associated with rapid reduction in IL-10 levels, while elevated IL-10 level was associated with disease recurrence. Elevated IL-10 levels and high IL-10/IL-6 ratio may aid in the diagnosis of PVRL. Aqueous IL-10 level monitoring can help assess the therapeutic response and indicate disease recurrence.

Analysis of Various Pickup Coil Designs in Nonmodule-Type GaN Power Semiconductors.

Gallium nitride (GaN) devices are advantageous over conventional Silicon (Si) devices in terms of their small size, low on-resistance, and high dv/dt characteristics; these ensure a high integrated density circuit configuration, high efficiency, and fast switching speed. Therefore, in the diagnosis and protection of a system containing a GaN power semiconductor, the transient state for accurate switch current measurement must be analyzed. The pick-up coil, as a current sensor for switch current measurement in a system comprising a surface-mount-device-type nonmodular GaN power semiconductor, has the advantages of a higher degree-of-freedom configuration for its printed circuit board, a relatively small size, and lower cost than other current sensors. However, owing to the fast switching characteristics of the GaN device, a bandwidth of hundreds MHz must be secured along with a coil configuration that must overcome the limitations of relatively low sensitivity of the conventional current sensor. This paper analyzes the pick-up coil sensor models that can achieve optimal bandwidth and sensitivity for switch current measurement in GaN based device. So four configurable pick-up coil models are considered and compared according to coil-parameter using mathematical methods, magnetic, and frequency-response analysis. Finally, an optimal coil model is proposed and validated using a double-pulse test.

Electroretinography and retinal microvascular changes in type 2 diabetes.

PURPOSE: To assess whether functional (electrophysiological) parameters are related to changes in the structural (microvascular) parameters in diabetic retina. METHODS: This prospective cohort study included 380 eyes of patients with diabetes mellitus (DM) and 160 eyes of healthy controls. We analysed the electroretinogram (ERG) parameters and vascular parameters acquired from optical coherence tomography (OCT) angiography according to the diabetic retinopathy (DR) severity from early to late stages of DR. RESULTS: After exclusion, 366 eyes of diabetes and 157 eyes of controls were included in the analysis. The mean age at enrolment was 65.4 ± 7.8 years, and 177 (33.84%) were male. The amplitude and implicit time of the rod and cone and combined response ERG b-wave were significantly reduced and prolonged in the eyes of patients with DM, compared to the controls. There was a positive correlation between the amplitude and vessel density (VD) of the superficial plexus and a negative correlation between the implicit time and superficial VD in the scotopic and combined response b-wave. Interestingly, there was no correlation between electrophysiological parameters and deep VD. These correlations between electrophysiological parameters and vascular parameters were not significant in the non-diabetic, healthy control group. CONCLUSIONS: Functional and structural impairments precede the clinical manifestation of DR. We also found that these neural impairments, evaluated by ERG, were correlated with superficial VD. However, this correlation was absent in the healthy and early DR groups. These findings carefully suggest that neuronal dysfunction is linked to vascular dysfunction in type 2 diabetes.

Molecular typing of Cyclospora cayetanensis in produce and clinical samples using targeted enrichment of complete mitochondrial genomes and next-generation sequencing.

BACKGROUND: Outbreaks of cyclosporiasis, a diarrheal illness caused by Cyclospora cayetanensis, have been a public health issue in the USA since the mid 1990's. In 2018, 2299 domestically acquired cases of cyclosporiasis were reported in the USA as a result of multiple large outbreaks linked to different fresh produce commodities. Outbreak investigations are hindered by the absence of standardized molecular epidemiological tools for C. cayetanensis. For other apicomplexan coccidian parasites, multicopy organellar DNA such as mitochondrial genomes have been used for detection and molecular typing. METHODS: We developed a workflow to obtain complete mitochondrial genome sequences from cilantro samples and clinical samples for typing of C. cayetanensis isolates. The 6.3 kb long C. cayetanensis mitochondrial genome was amplified by PCR in four overlapping amplicons from genomic DNA extracted from cilantro, seeded with oocysts, and from stool samples positive for C. cayetanensis by diagnostic methods. DNA sequence libraries of pooled amplicons were prepared and sequenced via next-generation sequencing (NGS). Sequence reads were assembled using a custom bioinformatics pipeline. RESULTS: This approach allowed us to sequence complete mitochondrial genomes from the samples studied. Sequence alterations, such as single nucleotide polymorphism (SNP) profiles and insertion and deletions (InDels), in mitochondrial genomes of 24 stool samples from patients with cyclosporiasis diagnosed in 2014, exhibited discriminatory power. The cluster dendrogram that was created based on distance matrices of the complete mitochondrial genome sequences, indicated distinct strain-level diversity among the 2014 C. cayetanensis outbreak isolates analyzed in this study. CONCLUSIONS: Our results suggest that genomic analyses of mitochondrial genome sequences may help to link outbreak cases to the source.

Choroidoscleral Interface Irregularity Index: A novel optical coherence tomography-based parameter in patients with epiretinal membrane.

This study aimed to assess the regularity of the choroidoscleral interface (CSI) using a novel parameter, CSI irregularity index, before and after epiretinal membrane (ERM) surgery. This study included 36 patients with idiopathic ERM who underwent pars plana vitrectomy and ERM removal. All subjects underwent ocular examinations at baseline and at 1, 2, 4, and 6 months after surgery. The regular contour of the CSI was found in 14 patients (38.9%); mean CSI irregularity index was 14.84 ± 11.01 in this group. The irregular contour of the CSI was found in 22 patients (61.1%); mean CSI irregularity index was 33.96 ± 20.64 in this group. The CSI irregularity index decreased gradually after ERM surgery, and was correlated with postoperative best-corrected visual acuity. The CSI irregularity index could serve as a surrogate marker to quantitatively represent the CSI morphology. We observed the gradual decrease of the CSI irregularity index after ERM surgery in quantitative manner. This study showed correlations between the CSI irregularity index and visual outcomes after ERM surgery. Our results suggest that the CSI irregularity index might be an intuitive anatomic indicator of the CSI and might be useful as a possible prognostic marker for patients undergoing ERM surgery.

USE OF CHOROIDAL VASCULARITY INDEX FOR CHOROIDAL STRUCTURAL EVALUATION IN CENTRAL SEROUS CHORIORETINOPATHY WITH CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To evaluate choroidal vascular structure in eyes with central serous chorioretinopathy (CSC) by assessing the choroidal vascular index (CVI). METHODS: We retrospectively analyzed the medical records of 117 eyes with CSC. Subjects were divided into 4 groups according to clinical characteristics: 1) acute CSC (N = 29), 2) non-neovascularized chronic CSC without flat irregular pigment epithelial detachment (N = 49), 3) non-neovascularized chronic CSC with flat irregular pigment epithelial detachment (N = 21), and 4) chronic CSC with choroidal neovascularization (N = 18). Subfoveal choroidal area (1,500 mm) of swept source optical coherence tomography scans were divided into luminal and stromal areas by the image binarization technique. The CVI was defined as the ratio of the luminal to the total subfoveal choroidal area. RESULTS: The CVI was significantly lower in eyes of Group 4 than those of other groups (all P < 0.05). The subfoveal choroidal thickness was significantly lower in Group 4 than in Groups 1 and 2 (P < 0.05), but regression analysis showed no association with the CVI. CONCLUSION: Decreased CVI may reflect choroidal vascular structure changes in eyes with choroidal neovascularization complicating CSC. These findings suggest that the CVI could be useful for evaluating choroidal vascular changes in eyes with CSC.

Polydopamine-doped conductive polymer microelectrodes for neural recording and stimulation.

BACKGROUND: Microelectrodes have been widely used to detect and modulate the activities of neuronal networks. Various materials have been applied to microelectrode fabrication, and the conductive polymer is one of the most intensively explored material. The properties of conductive polymer highly depend on the incorporated material, so selecting it is essential. The mussel-inspired biomolecule, polydopamine (pDA), is known to provide unique chemical and mechanical properties to biological interfaces. NEW METHOD: pDA was incorporated into poly(3,4-ethylenedioxythiophene) (PEDOT) resulting in polydopamine PEDOT hybrid (PEDOT/pDA) microelectrode by an electrochemical deposition method. The electrical properties, such as impedance, charge storage capacity (CSC), and charge injection limit (CIL), of PEDOT/pDA microelectrodes, were characterized. RESULTS: PEDOT/pDA microelectrodes had low impedance, high CSC, and high CIL, which are prerequisite for neuronal signal recording and stimulation. Then, neuronal recordings and electrical stimulations were conducted to verify the functionality of the PEDOT/pDA microelectrodes. Spontaneous and evoked extracellular neuronal signals were successfully measured from cultured rat hippocampal neuronal networks, and the recorded signals showed excellent signal-to-noise ratio for the detection of extracellular spikes. COMPARISON WITH EXISTING METHODS: Compared with existing conductive polymer based neural electrodes, the PEDOT/pDA microelectrode had chemically functional material, pDA, embedded in the electrode, while it had comparable level of impedance and CSC and CIL for neural stimulation and recordings. CONCLUSIONS: We have shown that it is possible to fabricate a microelectrode array of pDA doped PEDOT microelectrodes and validated its performance for neuronal signal recording and electrical stimulation. The PEDOT/pDA microelectrode with excellent electrical performance and biocompatibility will be a promising tool for studying neuronal networks.

Correlation of systemic arterial stiffness with changes in retinal and choroidal microvasculature in type 2 diabetes.

This study was conducted to assess whether systemic arterial stiffness, indicated by cardio-ankle vascular index (CAVI), is related to changes in the microvasculature of the retina and choroid in diabetes mellitus (DM). This study included 113 patients with a confirmed diagnosis of type-2 DM. Among them, 18 patients did not have diabetic retinopathy (DR), 71 had non-proliferative DR (NPDR), and 24 had proliferative DR (PDR). The mean CAVI was 7.58 ± 1.41 in no DR, 8.72 ± 1.47 in NPDR, and 8.43 ± 1.25 in PDR group. Of the 113 eyes, 42 (37.2%) were classified as abnormal CAVI group (CAVI ≥ 9). This group had significantly higher cardiac autonomic neuropathy risk index score, decreased central choroidal thickness, and decreased choroidal vascularity index (CVI). Deep foveal avascular zone area was higher in the abnormal CAVI group. After adjustment for possible confounding factors, CAVI showed negative correlation with the CVI (r = -0.247, P = 0.013). In conclusion, there was a significant correlation between arteriosclerosis and choroidal vascular changes in DR. We suggest prompt ophthalmic evaluation in patients with systemic arteriosclerosis. If the ophthalmologist notes advanced DR, the patient should be referred to a cardiovascular clinic for detailed evaluation of systemic arteriosclerosis.

Comparative sequence analysis of Cyclospora cayetanensis apicoplast genomes originating from diverse geographical regions.

BACKGROUND: Cyclospora cayetanensis is an emerging coccidian parasite that causes endemic and epidemic diarrheal disease called cyclosporiasis, and this infection is associated with consumption of contaminated produce or water in developed and developing regions. Food-borne outbreaks of cyclosporiasis have occurred almost every year in the USA since the 1990s. Investigations of these outbreaks are currently hampered due to lack of molecular epidemiological tools for trace back analysis. The apicoplast of C. cayetanensis, a relict non-photosynthetic plastid with an independent genome, provides an attractive target to discover sequence polymorphisms useful as genetic markers for detection and trace back analysis of the parasite. Distinct differences in the apicoplast genomes of C. cayetanensis could be useful in designing advanced molecular methods for rapid detection and, subtyping and geographical source attribution, which would aid outbreak investigations and surveillance studies. METHODS: To obtain the genome sequence of the C. cayetanensis apicoplast, we sequenced the C. cayetanensis genomic DNA extracted from clinical stool samples, assembled and annotated a 34,146 bp-long circular sequence, and used this sequence as a reference genome in this study. We compared the genome and the predicted proteome to the data available from other apicomplexan parasites. To initialize the search for genetic markers, we mapped the raw sequence reads from an additional 11 distinct clinical stool samples originating from Nepal, New York, Texas, and Indonesia to the apicoplast reference genome. RESULTS: We identified several high quality single nucleotide polymorphisms (SNPs) and small insertion/deletions spanning the apicoplast genome supported by extensive sequencing reads data, and a 30 bp sequence repeat at the terminal spacer region in a Nepalese sample. The predicted proteome consists of 29 core apicomplexan peptides found in most of the apicomplexans. Cluster analysis of these C. cayetanensis apicoplast genomes revealed a familiar pattern of tight grouping with Eimeria and Toxoplasma, separated from distant species such as Plasmodium and Babesia. CONCLUSIONS: SNPs and sequence repeats identified in this study may be useful as genetic markers for identification and differentiation of C. cayetanensis isolates found and could facilitate outbreak investigations.

Electro-optical Neural Platform Integrated with Nanoplasmonic Inhibition Interface.

Engineering of neural interfaces with nanomaterials for remote manipulation facilitates the development of platforms for the study and treatment of brain disorders, yet extending their capability to inhibiting the electrical activities of unmodified neurons has been difficult. Here we report the development of an electro-optical neural platform integrated with gold nanorods for simultaneous electrical excitation and readout, and photothermal inhibition of neural activities. A monolayer of gold nanorods was placed at the electrode-neuron interfaces of a microelectrode array for photothermal stimulation of neural activities. This nanoplasmonic interface interacted well with neurons and metal electrodes without affecting the biological and electrical properties. We demonstrated that spontaneous firing of neurons and their signal propagation along the neurites evoked by electrical stimulation were optically inhibited on this neural platform. We believe that our platform could be an alternative to the optogenetic approach and may ultimately be applied to prosthetic devices based on optical neuromodulation.

Electrochemical layer-by-layer approach to fabricate mechanically stable platinum black microelectrodes using a mussel-inspired polydopamine adhesive.

OBJECTIVE: Platinum black (PtBK) has long been used for microelectrode fabrication owing to its high recording performance of neural signals. The porous structure of PtBK enlarges the surface area and lowers the impedance, which results in background noise reduction. However, the brittleness of PtBK has been a problem in practice. In this work, we report mechanically stable PtBK microelectrodes using a bioinspired adhesive film, polydopamine (pDA), while maintaining the low impedance of PtBK. APPROACH: The pDA layer was incorporated into the PtBK structure through electrochemical layer-by-layer deposition. Varying the number of layers and the order of materials, multi-layered pDA-PtBK hybrids were fabricated and the electrical properties, both impedance and charge injection limit, were evaluated. MAIN RESULTS: Multilayered pDA-PtBK hybrids had electrical impedances as low as PtBK controls and charge injection limit twice larger than controls. For the 30 min-ultrasonication agitation test, impedance levels rarely changed for some of the pDA-PtBK hybrids indicating that the pDA improved the mechanical property of the PtBK structures. The pDA-PtBK hybrid microelectrodes readily recorded neural signals of cultured hippocampal neurons, where background noise levels and signal-to-noise were 2.43 âˆ¼ 3.23 µVrms and 28.4 âˆ¼ 69.1, respectively. SIGNIFICANCE: The developed pDA-PtBK hybrid microelectrodes are expected to be applicable to neural sensors for neural prosthetic studies.