The effect of duration between sessions on microperimetric biofeedback training in patients with maculopathies.

Aim of this study was to explore the optimal training interval and times of microperimetric biofeedback training (MBFT) in maculopathies. Twenty-nine patients with maculopathies were divided into two groups: daily training (Group A) or alternate daily training (Group B). Both groups underwent 15 MBFT sessions. We compared the BCVA, reading speed, and fixation stability at baseline, after 5, 10, 15 sessions. After 15 sessions of MBFT, all visual parameters in both groups improved. There was a significant increase in BCVA after 5 sessions in both groups (P=0.016, and P<0.001 respectively), but Group A showed further improvement after 10 sessions (P<0.001). Regarding reading speed, Group A showed significant improvement from baseline after 15 sessions(P=0.020), Group B improved significantly after 5 sessions (P=0.047) and continued to improve after 10 sessions (P=0.030). Additionally, P1 and LgBCEA of Group A significantly improved after 10 sessions (P=0.001, and P=0.001 respectively), while Group B significantly improved after 5 sessions (P=0.002, and P<0.001 respectively). There was no significant difference in visual outcomes between the two groups (P>0.05) except LgBCEA (P=0.046) after 15 sessions. We concluded that the both MBFT frequencies are effective at improving vision and quality of life in patients with maculopathies. The alternate daily training group showed less time-dependent of improvement in all parameters and a greater benefit in fixation stability. Ten sessions are the optimal number of treatment sessions for alternate daily training.

IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition.

The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients and modulated by exoglycosidase digestion. Taken together, this work links the IgM N-glycosylation with COVID-19 severity and highlights the need to understand IgM glycosylation and downstream immune function during human disease.

Host glycosylation of immunoglobulins impairs the immune response to acute Lyme disease.

BACKGROUND: Lyme disease is caused by the bacteria Borreliella burgdorferi sensu lato (Bb) transmitted to humans from the bite of an infected Ixodes tick. Current diagnostics for Lyme disease are insensitive at the early disease stage and they cannot differentiate between active infections and people with a recent history of antibiotic-treated Lyme disease. METHODS: Machine learning technology was utilized to improve the prediction of acute Lyme disease and identify sialic acid and galactose sugar structures (N-glycans) on immunoglobulins associated specifically at time points during acute Lyme disease time. A plate-based approach was developed to analyze sialylated N-glycans associated with anti-Bb immunoglobulins. This multiplexed approach quantitates the abundance of Bb-specific IgG and the associated sialic acid, yielding an accuracy of 90% in a powered study. FINDINGS: It was demonstrated that immunoglobulin sialic acid levels increase during acute Lyme disease and following antibiotic therapy and a 3-month convalescence, the sialic acid level returned to that found in healthy control subjects (p < 0.001). Furthermore, the abundance of sialic acid on Bb-specific IgG during acute Lyme disease impaired the host's ability to combat Lyme disease via lymphocytic receptor FcγRIIIa signaling. After enzymatically removing the sialic acid present on Bb-specific antibodies, the induction of cytotoxicity from acute Lyme disease patient antigen-specific IgG was significantly improved. INTERPRETATION: Taken together, Bb-specific immunoglobulins contain increased sialylation which impairs the host immune response during acute Lyme disease. Furthermore, this Bb-specific immunoglobulin sialyation found in acute Lyme disease begins to resolve following antibiotic therapy and convalescence. FUNDING: Funding for this study was provided by the Coulter-Drexel Translational Research Partnership Program as well as from a Faculty Development Award from the Drexel University College of Medicine Institute for Molecular Medicine and Infectious Disease and the Department of Microbiology and Immunology.

IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition.

The glycosylation of IgG plays a critical role during human SARS-CoV-2, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during acute viral infection in humans. In vitro evidence suggests that the glycosylation of IgM inhibits T cell proliferation and alters complement activation rates. The analysis of IgM N-glycosylation from healthy controls and hospitalized COVID-19 patients reveals that mannosylation and sialyation levels associate with COVID-19 severity. Specifically, we find increased di- and tri-sialylated glycans and altered mannose glycans in total serum IgM in severe COVID-19 patients when compared to moderate COVID-19 patients. This is in direct contrast with the decrease of sialic acid found on the serum IgG from the same cohorts. Moreover, the degree of mannosylation and sialylation correlated significantly with markers of disease severity: D-dimer, BUN, creatinine, potassium, and early anti-COVID-19 amounts of IgG, IgA, and IgM. Further, IL-16 and IL-18 cytokines showed similar trends with the amount of mannose and sialic acid present on IgM, implicating these cytokines' potential to impact glycosyltransferase expression during IgM production. When examining PBMC mRNA transcripts, we observe a decrease in the expression of Golgi mannosidases that correlates with the overall reduction in mannose processing we detect in the IgM N-glycosylation profile. Importantly, we found that IgM contains alpha-2,3 linked sialic acids in addition to the previously reported alpha-2,6 linkage. We also report that antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients. Taken together, this work links the immunoglobulin M N-glycosylation with COVID-19 severity and highlights the need to understand the connection between IgM glycosylation and downstream immune function during human disease.

Three machine learning algorithms and their utility in exploring risk factors associated with primary cesarean section in low-risk women: A methods paper.

Machine learning, a branch of artificial intelligence, is increasingly used in health research, including nursing and maternal outcomes research. Machine learning algorithms are complex and involve statistics and terminology that are not common in health research. The purpose of this methods paper is to describe three machine learning algorithms in detail and provide an example of their use in maternal outcomes research. The three algorithms, classification and regression trees, least absolute shrinkage and selection operator, and random forest, may be used to understand risk groups, select variables for a model, and rank variables' contribution to an outcome, respectively. While machine learning has plenty to contribute to health research, it also has some drawbacks, and these are discussed as well. To provide an example of the different algorithms' function, they were used on a completed cross-sectional study examining the association of oxytocin total dose exposure with primary cesarean section. The results of the algorithms are compared to what was done or found using more traditional methods.

Air tamponade in retinal detachment surgery followed by ultra-widefield fundus imaging system.

AIM: To report the surgical result of pars plana vitrectomy (PPV) with air tamponade for rhegmatogenous retinal detachment (RRD) by ultra-widefield fundus imaging system. METHODS: Of 25 consecutive patients (25 eyes) with fresh primary RRD and causative retinal break and vitreous traction were presented. All the patients underwent PPV with air tamponade. Visual acuity (VA) was examined postoperatively and images were captured by ultra-widefield scanning laser ophthalmoscope system (Optos). RESULTS: Initial reattachment was achieved in 25 cases (100%). The air volume was >60% on the postoperative day (POD) 1. The ultra-widefield images showed that the retina was reattached in all air-filled eyes postoperatively. The retinal break and laser burns in the superior were detected in 22 of 25 eyes (88%). A missed retinal hole was found under intravitreal air bubble in 1 case (4%). The air volume was range from 40% to 60% on POD 3. A double-layered image was seen in 25 of 25 eyes with intravitreal gas. Retinal breaks and laser burns around were seen in the intravitreal air. On POD 7, small bubble without effect was seen in 6 cases (24%) and bubble was completely disappeared in 4 cases (16%). Small oval bubble in the superior area was observed in 15 cases (60%). There were no missed and new retinal breaks and no retinal detachment in all cases on the POD 14 and 1mo and last follow-up. Air disappeared completely on a mean of 9.84d postoperatively. The mean final postoperative best-corrected visual acuity (BCVA) was 0.35 logMAR. Mean final postoperative BCVA improved significantly relative to mean preoperative (P<0.05). Final VA of 0.3 logMAR or better was seen in 13 eyes. CONCLUSION: PPV with air tamponade is an effective management for fresh RRD with superior retinal breaks. The ultra-widefield fundus imaging can detect postoperative retinal breaks in air-filled eyes. It would be a useful facility for follow-up after PPV with air tamponade. Facedown position and acquired visual rehabilitation may be shorten.

[Multifocal electroretinography for therapeutic effect evaluation of intravitreal injection Lucentis for wet age-related macular degeneration].

OBJECTIVE: To evaluate the changes in retinal functions using multifocal electroretinography (mfERG) following intravitreal injection of Lucentis for treatment of wet age-related macular degeneration. METHODS: This prospective study was conducted in 14 patients (9 men and 5 women, 14 eyes) with wet age-related macular degeneration receiving treatment with intravitreal injections of ranibizumab (Lucentis) in our hospital between October, 2014 and January, 2016. All the patients received the treatment following a 1+PRN protocol and after the initial injection, the patients were followed up monthly for 6 months to decide if additional injections were needed. The corrected visual acuity and mfERG findings of the patients were assessed before and at l, 3 and 6 months after the initial injection. RESULTS: At the last follow-up, the patients received injections for a mean of 2.86∓1.58 times. The best corrected visual acuity (BCVA) at 1 month after the initial treatment was not significantly different from that before treatment (P=0.07), but showed significant improvements at 3 and 6 months (P<0.05). In mfERG, the implicit time of the 6 rings showed no significant decrease after the treatment, but the amplitude density of P1 and N1 in rings 1 and 2 improved significantly at 1, 3, and 6 months after the initial injection (P<0.05). CONCLUSION: Multifocal electroretinography can serve as a useful modality for evaluating visual function changes in patients receiving intravitreal injection of Lucentis for wet age-related macular degeneration.

[Expression of Bcl-2 and Bax on retinal with a rat model for ocular ischemic syndrome].

OBJECTIVE: To tell the difference of Bcl-2 and Bax expression on the retina between the ocular ischemic syndrome group and the sham group. METHODS: Experimental study. To establish the ocular ischemic syndrome model by bilateral common carotid arteries obliteration (BCCAO) in BN rats. Twenty BN rats were divided into two groups randomly: 12 in the model group and 8 in the sham group. In model group, midline incised in the neck and bilateral common carotid artery obliterated. While in the sham group, midline incised in the neck with no obliteration. Pupillary reflex were detected in both groups. After 1 month, rats underwent fundus fluorescein angiography (FFA) examination. Optical coherence tomography (OCT) was used to measure and tell the retina thickness difference in both groups. Expression of Bcl-2 and Bax on rat retina and change of the Bcl-2/Bax ratio were detected by immunohistochemical staining. Chisquare test was used for classification variable, two independent samples T test was used for quantitative data. RESULTS: Compared to the sham group, only 1 eye of BCCAO group maintained its direct pupillary reflex, other eyes of the group appeared either lost or weakened their direct pupillary reflex. However, all rats in the sham group maintained their pupillary reflex. FFA showed that in the BCCAO group, retinal circulation time was significantly longer than it was in the sham group (aterial phase:t=6.19,P<0.01; arteriovenous phase:t=8.24,P<0.01; venous phase:t=2.73,P<0.05). And in the model group, the background choroidal patchy hypofluorescence and typical arterial forward phenomenon in the early phase of arterial time were observed. OCT showed that in the model group, an obvious decrease of the thickness of neuroepithelial layer of retina was observed, which was (195.67±8.84) µm in the model group and (219.31± 6.92) µm in the sham group. It had statistically significant difference (P<0.05). Immunohistochemical staining results showed imbalance of Bcl-2, Bax expression on rat retina. Compared with the sham group, expression level of bax which was (5.67±0.84) µm in the model group was significantly increased (P<0.05) , while it was (2.34 ± 0.57) µm in the sham group. There was no significant difference (P>0.05) in Bcl-2 expression in both groups, which was (5.61±0.98) µm in the model group and which was (5.63±0.88) µm in the sham group. And Bcl-2/Bax ratio was observed statistically significant decreased (P<0.05) in the BCCAO group compared with that in the sham group, which was (1.01 ± 0.23) in the model group, and which was (2.47±0.47) in the sham group. CONCLUSIONS: BCCAO of rats lead to the injury of retina function, diminish of retinal thickness, imbalance of Bax and Bcl-2 expression.