Effect of Yoga-based breathing practices on depression, anxiety, stress, and fear of COVID-19 positive hospitalized patients: A randomized controlled trial.

BACKGROUND: COVID-19 infection has an impact on the mental state of patients and requires attention to mental health care. OBJECTIVE: The aim of this study is to assess the effect of Yoga-based breathing practices on the mental state of patients with COVID-19. MATERIAL AND METHODS: A randomized controlled trial was conducted with63 patients (male=46) who were RT-PCR positive for COVID-19 and hospitalized with asymptomatic (RT-PCR positive but no symptoms), mild (febrile, body ache, pharyngitis, nonproductive cough), and moderate (SpO2< 92%) symptoms assigned in the yoga (n=32) and control group (n=31). The study was conducted at Atharva Multispecialty Hospital and Research Center, North India. The yoga group received Yoga-based breathing practices twice a day for ten days in addition to conventional care, and the control group was advised not to do the practice. The Depression Anxiety and Stress scale (DASS-21) and fear of COVID-19 were assessed at baseline and after 10 days. Repeated measures ANOVA with Bonferroni correction was used to assess between and within subjects' effects. RESULTS: The experimental group had better scores for depression, anxiety, stress, total DASS scores, and fear of COVID-19 (p<0.001) when compared with the control group. Within the group, analyses demonstrated improved scores in all domains in the yoga group (p<0.001) by the end of the intervention. In contrast, the control group improved only in stress scores (p=0.002), total DASS scores (p=0.012), and fear of COVID-19 (p=0.039). There are no adverse effects seen with Yoga-based breathing practices in these patients. CONCLUSION: Yoga-based breathing practices have been found to have positive impact on mental health among COVID-19-positive patients during hospitalization. TRIAL REGISTRY NUMBER CTRI: CTRI/2022/03/041071 Clinical Trials-Registry in India.

Mechanistic basis for rescuing hypertrophic cardiomyopathy with myosin regulatory light chain phosphorylation.

We investigated the impact of the phosphomimetic (Ser15 → Asp15) myosin regulatory light chain (S15D-RLC) on the Super-Relaxed (SRX) state of myosin using previously characterized transgenic (Tg) S15D-D166V rescue mice, comparing them to the Hypertrophic Cardiomyopathy (HCM) Tg-D166V model and wild-type (WT) RLC mice. In the Tg-D166V model, we observed a disruption of the SRX state, resulting in a transition from SRX to DRX (Disordered Relaxed) state, which explains the hypercontractility of D166V-mutated myosin motors. The presence of the S15D moiety in Tg-S15D-D166V mice restored the SRX/DRX balance to levels comparable to Tg-WT, thus mitigating the hypercontractile behavior associated with the HCM-D166V mutation. Additionally, we investigated the impact of delivering the S15D-RLC molecule to the hearts of Tg-D166V mice via adeno-associated virus (AAV9) and compared their condition to AAV9-empty vector-injected or non-injected Tg-D166V animals. Tg-D166V mice injected with AAV9 S15D-RLC exhibited a significantly higher proportion of myosin heads in the SRX state compared to those injected with AAV9 empty vector or left non-injected. No significant effect was observed in Tg-WT hearts treated similarly. These findings suggest that AAV9-delivered phosphomimetic S15D-RLC modality mitigates the abnormal Tg-D166V phenotype without impacting the normal function of Tg-WT hearts. Global longitudinal strain analysis supported these observations, indicating that the S15D moiety can alleviate the HCM-D166V phenotype by restoring SRX stability and the SRX ↔ DRX equilibrium.

Modified Osteotomy for TMJ Ankylosis in Paediatric Patients with Deficient Interpositional Temporalis Muscle Mass and Buccal Fat Pad - A case Series and Literature Review.

Ankylosis of the temporomandibular joint (TMJ) is a bony or fibrous fusion of the articular surfaces of the mandibular condyle and the glenoid fossa. Gap arthroplasty, Interpositional arthroplasty, Condyle reconstruction with autogenic or alloplastic grafts and total joint replacement are some common modalities of management. In this article, we discuss a series of three cases of unilateral TMJ ankylosis in paediatric patients, managed by gap arthroplasty using a modified osteotomy cut. The modification was adapted due to inadequate interpositionable temporalis muscle or buccal fat on the affected side and chances of adaptive remodelling of the CCG (Costochondral graft), if placed were rendered negative.

Acute Kidney Injury among Neonates with Perinatal Asphyxia in a Tertiary Care Centre.

Introduction: Perinatal asphyxia is a very common cause of morbidity and mortality in both term and preterm neonates and ranks the second most important cause of neonatal death. The incidence and importance of acute kidney injury in the neonatal period are becoming increasingly apparent. Early diagnosis and timely management of acute kidney injury is very important in these newborns to avoid other long-term adverse events. This study aimed to find out the prevalence of acute kidney injury among neonates with perinatal asphyxia in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted at the neonatal intensive care unit and nursery in a tertiary care hospital of Eastern Nepal from 1 November 2021 to 31 October 2022 after obtaining ethical approval from the Institutional Review Committee. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 97 neonates, the prevalence of acute kidney injury was seen among 60 (61.86%) (50.25-69.75, 95% Confidence Interval) neonates. Out of which 42 (70%) were males and 18 (30%) were female. Conclusions: The prevalence of acute kidney injury among neonates with perinatal asphyxia was found to be higher than other studies done in a similar setting. Keywords: acute kidney injury; neonates; prevalence.

Factors Associated With Healthcare Clinician Stress and Resilience: A Scoping Review.

GOAL: Clinician stress and resilience have been the subjects of significant research and interest in the past several decades. We aimed to understand the factors that contribute to clinician stress and resilience in order to appropriately guide potential interventions. METHODS: We conducted a scoping review (n = 42) of published reviews of research on clinician distress and resilience using the methodology of Peters and colleagues (2020). Our team examined these reviews using the National Academy of Medicine's framework for clinician well-being and resilience. PRINCIPAL FINDINGS: We found that organizational factors, learning/practice environment, and healthcare responsibilities were three of the top four factors identified in the reviews as contributing to clinician distress. Learning/practice environment and organizational factors were two of the top four factors identified in the reviews as contributing to their resilience. PRACTICAL APPLICATIONS: Clinicians continue to face numerous external challenges that complicate their work. Further research, practice, and policy changes are indicated to improve practice environments for healthcare clinicians. Healthcare leaders need to promote resources for organizational and system-level changes to improve clinician well-being.

Carbon quantum dot-nanocomposite hydrogel as Denovo Nexus in rapid chondrogenesis.

The incapability of cartilage to naturally regenerate and repair chronic muscular injuries urges the development of competent bionic rostrums. There is a need to explore faster strategies for chondrogenic engineering using mesenchymal stem cells (MSCs). Along these lines, rapid chondrocyte differentiation would benefit the transplantation demand affecting osteoarthritis (OA) and rheumatoid arthritis (RA) patients. In this report, a de novo nanocomposite was constructed by integrating biogenic carbon quantum dot (CQD) filler into synthetic hydrogel prepared from dimethylaminoethyl methacrylate (DMAEMA) and acrylic acid (AAc). The dominant structural integrity of synthetic hydrogel along with the chondrogenic differentiation potential of garlic peel derived CQDs led to faster chondrogenesis within 14 days. By means of extensive chemical and morphological characterization techniques, we illustrate that the hydrogel nanocomposite possesses lucrative features to influence rapid chondrogenesis. These results were further corroborated by bright field imaging, Alcian blue staining and Masson trichome staining. Thus, this stratagem of chondrogenic engineering conceptualizes to be a paragon in clinical wound care for the rapid manufacturing of chondrocytes.

Chemical synthesis of the O-antigen repeating unit of Actinobacillus actinomycetemcomitans serotype f.

Herein, we report the total synthesis of the trisaccharide repeating unit of the O-antigen of Actinobacillus actinomycetemcomitans serotype f. The trisaccharide comprising of α-(1-2) and α-(1-3)-linked L-rhamnopyranosides backbone with the latter rhamnose containing a branching N-acetyl-d-galactosaminopyranoside at the C2-O via a ß-glycosidic bond was synthesized by two methods. Initially, the protected trisaccharide has been synthesized by step-wise assembly of the monosaccharide building blocks and subsequently the former was synthesized by the one-pot assembly of the latter components. The synthesized trisaccharide contains an aminoethyl linker appended as an O-glycoside at the reducing end, thereby providing scope for further conjugation for different applications.

Improved Cardiac Performance and Decreased Arrhythmia in Hypertrophic Cardiomyopathy With Non-ß-Blocking R-Enantiomer Carvedilol.

BACKGROUND: Hypercontractility and arrhythmia are key pathophysiologic features of hypertrophic cardiomyopathy (HCM), the most common inherited heart disease. ß-Adrenergic receptor antagonists (ß-blockers) are the first-line therapy for HCM. However, ß-blockers commonly selected for this disease are often poorly tolerated in patients, where heart-rate reduction and noncardiac effects can lead to reduced cardiac output and fatigue. Mavacamten, myosin ATPase inhibitor recently approved by the US Food and Drug Administration, has demonstrated the ability to ameliorate hypercontractility without lowering heart rate, but its benefits are so far limited to patients with left ventricular (LV) outflow tract obstruction, and its effect on arrhythmia is unknown. METHODS: We screened 21 ß-blockers for their impact on myocyte contractility and evaluated the antiarrhythmic properties of the most promising drug in a ventricular myocyte arrhythmia model. We then examined its in vivo effect on LV function by hemodynamic pressure-volume loop analysis. The efficacy of the drug was tested in vitro and in vivo compared with current therapeutic options (metoprolol, verapamil, and mavacamten) for HCM in an established mouse model of HCM (Myh6R403Q/+ and induced pluripotent stem cell (iPSC)-derived cardiomyocytes from patients with HCM (MYH7R403Q/+). RESULTS: We identified that carvedilol, a ß-blocker not commonly used in HCM, suppresses contractile function and arrhythmia by inhibiting RyR2 (ryanodine receptor type 2). Unlike metoprolol (a ß1-blocker), carvedilol markedly reduced LV contractility through RyR2 inhibition, while maintaining stroke volume through α1-adrenergic receptor inhibition in vivo. Clinically available carvedilol is a racemic mixture, and the R-enantiomer, devoid of ß-blocking effect, retains the ability to inhibit both α1-receptor and RyR2, thereby suppressing contractile function and arrhythmias without lowering heart rate and cardiac output. In Myh6R403Q/+ mice, R-carvedilol normalized hyperdynamic contraction, suppressed arrhythmia, and increased cardiac output better than metoprolol, verapamil, and mavacamten. The ability of R-carvedilol to suppress contractile function was well retained in MYH7R403Q/+ iPSC-derived cardiomyocytes. CONCLUSIONS: R-enantiomer carvedilol attenuates hyperdynamic contraction, suppresses arrhythmia, and at the same time, improves cardiac output without lowering heart rate by dual blockade of α1-adrenergic receptor and RyR2 in mouse and human models of HCM. This combination of therapeutic effects is unique among current therapeutic options for HCM and may particularly benefit patients without LV outflow tract obstruction.

Orthopedic Scaffolds: Evaluation of Structural Strength and Permeability of Fluid Flow via an Open Cell Neovius Structure for Bone Tissue Engineering.

The ability of bone to regenerate itself through mechanobiological responses is its dynamic property. Mechanical cues from a neighboring environment produce the structural strain to promote blood flow and bone marrow mobility that in turn aids the bone regeneration process. Occurrences of these phenomena are crucial for the success of metallic scaffolds implanted in the host bone tissue. Thus, permeability and fluid flow-induced wall shear stress (WSS) are two parameters that directly influence cell bioactivities inside a scaffold and are crucial for effective bone tissue regeneration. Given that the scaffolds shall be implanted in the body, permeability assessment was carried out using non-Newtonian fluid. In this work, the triply periodic minimal surface scaffolds with Neovius architectures were fabricated by using selective laser melting technology. The estimation of fluid flow was carried out using computational fluid dynamics (CFD) analysis with a non-Newtonian blood fluid model. Further, the structural strength of various open cell Neovius lattices was evaluated using a static compression test, and in vitro cell culture using Alamar blue assay was evaluated. Results revealed that the values of intrinsic blood flow permeability of the three-dimensional (3D)-printed open cell porous scaffold with Neovius architecture were of the same order of magnitude as those of human bone, ranging from 0.0025 × 10-9 to 0.0152 × 10-9 m2. The structural elastic modulus and compressive strength of NOCL40, NOCL50, and NOCL60 lattices range from 3.27 to 3.71 GPa and 194 to 205 MPa, respectively. All of the values are comparable to the human bone, thus making these lattices a suitable alternative for orthopedic applications.

A prophage tail-like protein facilitates the endophytic growth of Burkholderia gladioli and mounting immunity in tomato.

A prophage tail-like protein (Bg_9562) of Burkholderia gladioli strain NGJ1 possesses broad-spectrum antifungal activity, and it is required for the bacterial ability to forage over fungi. Here, we analyzed whether heterologous overexpression of Bg_9562 or exogenous treatment with purified protein can impart disease tolerance in tomato. The physiological relevance of Bg_9562 during endophytic growth of NGJ1 was also investigated. Bg_9562 overexpressing lines demonstrate fungal and bacterial disease tolerance. They exhibit enhanced expression of defense genes and activation of mitogen-activated protein kinases. Treatment with Bg_9562 protein induces defense responses and imparts immunity in wild-type tomato. The defense-inducing ability lies within 18-51 aa region of Bg_9562 and is due to sequence homology with the bacterial flagellin epitope. Interaction studies suggest that Bg_9562 is perceived by FLAGELLIN-SENSING 2 homologs in tomato. The silencing of SlSERK3s (BAK1 homologs) prevents Bg_9562-triggered immunity. Moreover, type III secretion system-dependent translocation of Bg_9562 into host apoplast is important for elicitation of immune responses during colonization of NGJ1. Our study emphasizes that Bg_9562 is important for the endophytic growth of B. gladioli, while the plant perceives it as an indirect indicator of the presence of bacteria to mount immune responses. The findings have practical implications for controlling plant diseases.

Effects of Nadishodhana and Bhramari Pranayama on heart rate variability, auditory reaction time, and blood pressure: A randomized clinical trial in hypertensive patients.

BACKGROUND: Hypertension (HTN) is a chronic elevation of arterial blood pressure (BP) due to environmental and lifestyle factors. The lifelong treatment protocol causes poor adherence to anti-hypertensive drugs. Nadi Shodhana and Bhramari pranayama are the most effective yogic treatment for the management of HTN. OBJECTIVES: This study was done to assess and compare the immediate effect of Nadi Shodhana and Bhramari Pranayama on HRV and ART in hypertensive individuals. Thus, to understand the effectiveness of specific pranayama on hypertension. METHODOLOGY: This study is a randomized, comparative study design. The hundred participants were recruited into two groups 1 (n = 50) and 2 (n = 50). The study was conducted on pre-diagnosed patients with HTN, from the inpatient department of SDM Nature Cure Hospital, Shanthivana. Group 1 was asked to practice Nadi Shodhana Pranayama and Group-2 was asked to practice Bhramari Pranayama for 20 min. The patients were assessed for Heart Rate Variability & Auditory Reaction Time before and immediately after the intervention. RESULTS: Nadi Shodhana Pranayama showed a significant decrease in ART (p = 0.01) and Bhramari Pranayama showed a highly significant decrease in ART (p < 0.00001). Whereas there was no statistically significant difference in both the groups in HRV parameters. CONCLUSION: The study showed that both Nadi Shodhana and Bhramari Pranayama can be effective in balancing the sympathovagal tone. Thus, Nadi Shodhana and Bhramari Pranayama can be practised for the management of essential hypertension.

Nicotinic Acid Catabolism Modulates Bacterial Mycophagy in Burkholderia gladioli Strain NGJ1.

Burkholderia gladioli strain NGJ1 exhibits mycophagous activity on a broad range of fungi, including Rhizoctonia solani, a devastating plant pathogen. Here, we demonstrate that the nicotinic acid (NA) catabolic pathway in NGJ1 is required for mycophagy. NGJ1 is auxotrophic to NA and it potentially senses R. solani as a NA source. Mutation in the nicC and nicX genes involved in NA catabolism renders defects in mycophagy and the mutant bacteria are unable to utilize R. solani extract as the sole nutrient source. As supplementation of NA, but not FA (fumaric acid, the end product of NA catabolism) restores the mycophagous ability of ΔnicC/ΔnicX mutants, we anticipate that NA is not required as a carbon source for the bacterium during mycophagy. Notably, nicR, a MarR-type of transcriptional regulator that functions as a negative regulator of the NA catabolic pathway is upregulated in ΔnicC/ΔnicX mutant and upon NA supplementation the nicR expression is reduced to the basal level in both the mutants. The ΔnicR mutant produces excessive biofilm and is completely defective in swimming motility. On the other hand, ΔnicC/ΔnicX mutants are compromised in swimming motility as well as biofilm formation, potentially due to the upregulation of nicR. Our data suggest that a defect in NA catabolism alters the NA pool in the bacterium and upregulates nicR which in turn suppresses bacterial motility as well as biofilm formation, leading to mycophagy defects. IMPORTANCE Mycophagy is an important trait through which certain bacteria forage over fungal mycelia and utilize fungal biomass as a nutrient source to thrive in hostile environments. The present study emphasizes that nicotinic acid (NA) is important for bacterial motility and biofilm formation during mycophagy by Burkholderia gladioli strain NGJ1. Defects in NA catabolism potentially alter the cellular NA pool, upregulate the expression of nicR, a negative regulator of biofilm, and therefore suppress bacterial motility as well as biofilm formation, leading to mycophagy defects.

Prior optic neuritis detection on peripapillary ring scans using deep learning.

BACKGROUND: The diagnosis of multiple sclerosis (MS) requires demyelinating events that are disseminated in time and space. Peripapillary retinal nerve fiber layer (pRNFL) thickness as measured by optical coherence tomography (OCT) distinguishes eyes with a prior history of acute optic neuritis (ON) and may provide evidence to support a demyelinating attack. OBJECTIVE: To investigate whether a deep learning (DL)-based network can distinguish between eyes with prior ON and healthy control (HC) eyes using peripapillary ring scans. METHODS: We included 1033 OCT scans from 415 healthy eyes (213 HC subjects) and 510 peripapillary ring scans from 164 eyes with prior acute ON (140 patients with MS). Data were split into 70% training, 15% validation, and 15% test data. We included 102 OCT scans from 80 healthy eyes (40 HC) and 61 scans from 40 ON eyes (31 MS patients) from an independent second center. Receiver operating characteristic curve analyses with area under the curve (AUC) were used to investigate performance. RESULTS: We used a dilated residual convolutional neural network for the classification. The final network had an accuracy of 0.85 and an AUC of 0.86, whereas pRNFL only had an AUC of 0.77 in recognizing ON eyes. Using data from a second center, the network achieved an accuracy of 0.77 and an AUC of 0.90 compared to pRNFL, which had an AUC of 0.84. INTERPRETATION: DL-based disease classification of prior ON is feasible and has the potential to outperform thickness-based classification of eyes with and without history of prior ON.

Serum glial fibrillary acidic protein correlates with retinal structural damage in aquaporin-4 antibody positive neuromyelitis optica spectrum disorder.

BACKGROUND: Aquaporin-4 immunoglobulin-G positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy associated with optic neuritis (ON). Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an oligodendrocytopathy with a similar phenotype. Serum glial fibrillary acidic protein (sGFAP), an astrocyte-derived protein, is associated with disease severity in AQP4-IgG+ NMOSD. Serum neurofilament light (sNfL) indicates neuroaxonal damage. The objective was to investigate the association of sGFAP and sNfL with subclinical afferent visual system damage in clinically stable AQP4-IgG+ NMOSD and MOGAD patients. METHODS: In this cross-sectional study, clinically stable patients with AQP4-IgG+ NMOSD (N = 33) and MOGAD (N = 16), as diseased controls, underwent sGFAP and sNfL measurements by single molecule array, retinal optical coherence tomography and visually evoked potentials. RESULTS: Higher sGFAP concentrations were associated with thinner ganglion cell-inner plexiform layer (ß (95% confidence interval (CI)) = -0.75 (-1.23 to -0.27), p = 0.007) and shallower fovea (average pit depth: ß (95%CI) = -0.59 (-0.63 to -0.55), p = 0.020) in NMOSD non-ON eyes. Participants with pathological P100 latency had higher sGFAP (median [interquartile range]: 131.32 [81.10-179.34] vs. 89.50 [53.46-121.91] pg/ml, p = 0.024). In MOGAD, sGFAP was not associated with retinal structural or visual functional measures. CONCLUSIONS: The association of sGFAP with structural and functional markers of afferent visual system damage in absence of ON suggests that sGFAP may be a sensitive biomarker for chronic disease severity in clinically stable AQP4-IgG+ NMOSD.

Synthesis of the trisaccharide repeating unit of Stenotrophomonas maltophilia O6 antigen through step-wise and one-pot approaches.

Synthetic conjugate vaccines are an important area of research for the prevention and occurrence of diseases caused by Gram-negative bacteria. For the development of such vaccines, access to the pure and homogeneous oligosaccharide fragments of the bacterial cell surface polysaccharides are necessary. Stenotrophomonas maltophilia is a typical opportunistic Gram-negative bacteria that causes severe pulmonary and other infections; often in hospitalized patients. With the emergence of multidrug resistant strains and increased virulence, new therapeutic strategies are needed to combat the threat. Herein, we report the syntheses of the trisaccharide repeating unit of S. maltophilia O6 antigen through stepwise and one-pot assemblies of the trisaccharide. The target trisaccharide was appended with a 2-aminoethyl linker that could provide the opportunity for conjugation to carrier proteins for the synthesis of vaccine candidates.

N-Terminus Plays a Critical Role for Stabilizing the Filamentous Assembly and the Antifungal Activity of Bg_9562.

Bg_9562, a prophage tail-like protein was earlier shown to be required for bacterial mycophagy by Burkholderia gladioli strain NGJ1. The purified protein exhibited broad-spectrum antifungal activity; however, the structural and mechanistic details vis-à-vis its activity remained elusive. In this study, we have structurally characterized the protein Bg_9562 using negatively stained transmission electron microscopy, molecular modeling and mutagenesis. We find that Bg_9562 shows structural similarity to Gp13, a tail assembly chaperone. The transmission electron microscopy revealed that, Bg_9562 forms long flexible tubular structures. Molecular modeling of the filament like structure divulges that the inter subunit contacts are meditated largely through hydrophobic interactions. Using mutagenesis, we demonstrate that the N-terminal residues of the protein when deleted results in reduced activity and destabilization of filament formation. Overall, structure-function analysis opens up avenues for further utilization of the protein as a potent antifungal molecule. IMPORTANCE Burkholderia gladioli strain NGJ1, isolated from healthy rice seedling, was earlier demonstrated to have mycophagous properties on a broad range of fungi, including Rhizoctonia solani, a causal agent of deadly sheath blight disease of rice. The purified Bg_9562 protein exerts broad-spectrum antifungal activity. The protein also inhibits the growth of laboratory strain of Candida, an opportunistic human pathogen. In this study, we structurally characterize Bg_9562 using a combination of negative staining transmission electron microscopy, molecular modeling, mutagenesis, and functional antifungal assay. We show that the protein assembles into long filament like structures stabilized by N-terminus residues and this region is important for its activity. Our study has implications in utilizing Bg_9562 or its derivatives as antifungal molecule(s) which will provide environmentally friendly control of fungal diseases of plants and animals.

Central Macular Topographic and Volumetric Measures: New Biomarkers for Detection of Glaucoma.

Purpose: To test the hypothesis that newly developed shape measures using optical coherence tomography (OCT) macular volume scans can discriminate patients with perimetric glaucoma from healthy subjects. Methods: OCT structural measures defining macular topography and volume were recently developed based on cubic Bézier curves. We exported macular volume scans from 135 eyes with glaucoma (133 patients) and 155 healthy eyes (85 subjects) and estimated global and quadrant-based measures. The best subset of measures to predict glaucoma was explored with a gradient boost model (GBM) with subsequent logistic regression. Accuracy and area under receiver operating curves (AUC) were the primary metrics. In addition, we separately investigated model performance in 66 eyes with mild glaucoma (mean deviation ≥ -6 dB). Results: Average (±SD) 24-2 mean deviation was -8.2 (±6.1) dB in eyes with glaucoma. The main predictive measures for glaucoma were temporal inferior rim height, nasal inferior pit volume, and temporal inferior pit depth. Lower values for these measures predicted higher risk of glaucoma. Sensitivity, specificity, and AUC for discriminating between healthy and glaucoma eyes were 81.5% (95% CI = 76.6-91.9%), 89.7% (95% CI = 78.7-94.2%), and 0.915 (95% CI = 0.882-0.948), respectively. Corresponding metrics for mild glaucoma were 84.8% (95% CI = 72.1%-95.5%), 85.8% (95% CI = 87.1%-97.4%), and 0.913 (95% CI = 0.867-0.958), respectively. Conclusions: Novel macular shape biomarkers detect early glaucoma with clinically relevant performance. Such biomarkers do not depend on intraretinal segmentation accuracy and may be helpful in eyes with suboptimal macular segmentation. Translational Relevance: Macular shape biomarkers provide valuable information for detection of early glaucoma and may provide additional information beyond thickness measurements.

Intraretinal Layer Segmentation Using Cascaded Compressed U-Nets.

Reliable biomarkers quantifying neurodegeneration and neuroinflammation in central nervous system disorders such as Multiple Sclerosis, Alzheimer's dementia or Parkinson's disease are an unmet clinical need. Intraretinal layer thicknesses on macular optical coherence tomography (OCT) images are promising noninvasive biomarkers querying neuroretinal structures with near cellular resolution. However, changes are typically subtle, while tissue gradients can be weak, making intraretinal segmentation a challenging task. A robust and efficient method that requires no or minimal manual correction is an unmet need to foster reliable and reproducible research as well as clinical application. Here, we propose and validate a cascaded two-stage network for intraretinal layer segmentation, with both networks being compressed versions of U-Net (CCU-INSEG). The first network is responsible for retinal tissue segmentation from OCT B-scans. The second network segments eight intraretinal layers with high fidelity. At the post-processing stage, we introduce Laplacian-based outlier detection with layer surface hole filling by adaptive non-linear interpolation. Additionally, we propose a weighted version of focal loss to minimize the foreground-background pixel imbalance in the training data. We train our method using 17,458 B-scans from patients with autoimmune optic neuropathies, i.e., multiple sclerosis, and healthy controls. Voxel-wise comparison against manual segmentation produces a mean absolute error of 2.3 µm, outperforming current state-of-the-art methods on the same data set. Voxel-wise comparison against external glaucoma data leads to a mean absolute error of 2.6 µm when using the same gold standard segmentation approach, and 3.7 µm mean absolute error in an externally segmented data set. In scans from patients with severe optic atrophy, 3.5% of B-scan segmentation results were rejected by an experienced grader, whereas this was the case in 41.4% of B-scans segmented with a graph-based reference method. The validation results suggest that the proposed method can robustly segment macular scans from eyes with even severe neuroretinal changes.

Modular deep neural networks for automatic quality control of retinal optical coherence tomography scans.

Retinal optical coherence tomography (OCT) with intraretinal layer segmentation is increasingly used not only in ophthalmology but also for neurological diseases such as multiple sclerosis (MS). Signal quality influences segmentation results, and high-quality OCT images are needed for accurate segmentation and quantification of subtle intraretinal layer changes. Among others, OCT image quality depends on the ability to focus, patient compliance and operator skills. Current criteria for OCT quality define acceptable image quality, but depend on manual rating by experienced graders and are time consuming and subjective. In this paper, we propose and validate a standardized, grader-independent, real-time feedback system for automatic quality assessment of retinal OCT images. We defined image quality criteria for scan centering, signal quality and image completeness based on published quality criteria and typical artifacts identified by experienced graders when inspecting OCT images. We then trained modular neural networks on OCT data with manual quality grading to analyze image quality features. Quality analysis by a combination of these trained networks generates a comprehensive quality report containing quantitative results. We validated the approach against quality assessment according to the OSCAR-IB criteria by an experienced grader. Here, 100 OCT files with volume, circular and radial scans, centered on optic nerve head and macula, were analyzed and classified. A specificity of 0.96, a sensitivity of 0.97 and an accuracy of 0.97 as well as a Matthews correlation coefficient of 0.93 indicate a high rate of correct classification. Our method shows promising results in comparison to manual OCT grading and may be useful for real-time image quality analysis or analysis of large data sets, supporting standardized application of image quality criteria.

The alternative sigma factors, rpoN1 and rpoN2 are required for mycophagous activity of Burkholderia gladioli strain NGJ1.

Bacteria utilize RpoN, an alternative sigma factor (σ54) to grow in diverse habitats, including nitrogen-limiting conditions. Here, we report that a rice-associated mycophagous bacterium Burkholderia gladioli strain NGJ1 encodes two paralogues of rpoN viz. rpoN1 and rpoN2. Both of them are upregulated during 24 h of mycophagous interaction with Rhizoctonia solani, a polyphagous fungal pathogen. Disruption of either one of rpoNs renders the mutant NGJ1 bacterium defective in mycophagy, whereas ectopic expression of respective rpoN genes restores mycophagy in the complementing strains. NGJ1 requires rpoN1 and rpoN2 for efficient biocontrol to prevent R. solani to establish disease in rice and tomato. Further, we have identified 17 genes having RpoN regulatory motif in NGJ1, majority of them encode potential type III secretion system (T3SS) effectors, nitrogen assimilation, and cellular transport-related functions. Several of these RpoN regulated genes as well as certain previously reported T3SS apparatus (hrcC and hrcN) and effector (Bg_9562 and endo-ß-1,3-glucanase) encoding genes are upregulated in NGJ1 but not in ΔrpoN1 or ΔrpoN2 mutant bacterium, during mycophagous interaction with R. solani. This highlights that RpoN1 and RpoN2 modulate T3SS, nitrogen assimilation as well as cellular transport systems in NGJ1 and thereby promote bacterial mycophagy.