Progression of diabetic retinopathy following uncomplicated phacoemulsification: A prospective study from South India.

AIM: The aim of this study was to study the progression of diabetic retinopathy (DR) and macular edema in uncomplicated phacoemulsification in patients with diabetes mellitus with a follow-up of 6 months. METHODS: A prospective, nonrandomized study was conducted on patients with established or no DR in a known case of diabetes mellitus undergoing cataract surgery by phacoemulsification, with no intraoperative complications. Detailed ophthalmic evaluation including fundus examination was done in all cases, and DR staging was done. Optical coherence tomography and fundus fluorescein angiography were done in indicated cases. Fundus evaluation was done during the follow-up visits in 3 weeks, 3 months, and 6 months postsurgery and the tests were repeated if necessary. RESULTS: In the current study, there was a statistically significant improvement in best-corrected visual acuity after cataract surgery compared to the preoperative value. From the 330 eyes we analyzed, there was a progression of DR in only 18 eyes (5.45%) following phacoemulsification. There was a statistically significant increase in central macular thickness (CMT) at 3 weeks postoperative (433.82 ± 137.572) compared to that of the preoperative CMT (295.98 ± 97.959). From the 22 eyes which showed a progression of diabetic maculopathy, 11 eyes had developed new-onset macular edema following the cataract surgery, 11 eyes had progression of preexisting edema, and 4 of them had to undergo intravitreal anti-vascular endothelial growth factor injections as the treatment. CONCLUSION: The chance of progression of DR staging is low after uncomplicated phacoemulsification, on a short term. However, the chances of worsening of macular edema as well as worsening of proliferative stages should be kept in mind while advising a patient for cataract surgery.

Artificial intelligence chatbot performance in triage of ophthalmic conditions.

BACKGROUND: Timely access to human expertise for affordable and efficient triage of ophthalmic conditions is inconsistent. With recent advancements in publicly available artificial intelligence (AI) chatbots, the lay public may turn to these tools for triage of ophthalmic complaints. Validation studies are necessary to evaluate the performance of AI chatbots as triage tools and inform the public regarding their safety. OBJECTIVE: To evaluate the triage performance of AI chatbots for ophthalmic conditions. DESIGN: Cross-sectional study. SETTING: Single centre. PARTICIPANTS: Ophthalmology trainees, OpenAI ChatGPT (GPT-4), Bing Chat, and WebMD Symptom Checker. METHODS: Forty-four clinical vignettes representing common ophthalmic complaints were developed, and a standardized pathway of prompts was presented to each tool in March 2023. Primary outcomes were proportion of responses with the correct diagnosis listed in the top 3 possible diagnoses and proportion with correct triage urgency. Ancillary outcomes included presence of grossly inaccurate statements, mean reading grade level, mean response word count, proportion with attribution, and most common sources cited. RESULTS: The ophthalmologists in training, ChatGPT, Bing Chat, and the WebMD Symptom Checker listed the appropriate diagnosis among the top 3 suggestions in 42 (95%), 41 (93%), 34 (77%), and 8 (33%) cases, respectively. Triage urgency was appropriate in 38 (86%), 43 (98%), and 37 (84%) cases for ophthalmology trainees, ChatGPT, and Bing Chat, correspondingly. CONCLUSIONS: ChatGPT using the GPT-4 model offered high diagnostic and triage accuracy that was comparable with that of ophthalmology trainees with no grossly inaccurate statements. Bing Chat had lower accuracy and a tendency to overestimate triage urgency.

Dual orexin antagonist normalized sleep homeostatic drive, enhanced GABAergic inhibition, and suppressed seizures after traumatic brain injury.

STUDY OBJECTIVES: Traumatic brain injury (TBI) can result in posttraumatic epilepsy (PTE) and sleep disturbances. We hypothesized that treatment with sleep aids after TBI can ameliorate PTE. METHODS: CD-1 mice underwent controlled cortical impact (CCI), sham injury, or no craniotomy. Sham and CCI groups underwent a monthlong daily treatment with sleep aids including a dual orexin antagonist (DORA-22) or THIP (gaboxadol) or a respective vehicle starting on the day of CCI. We performed continuous EEG (electroencephalography) recordings at week 1 and months 1, 2, and 3 for ~1 week each time. Seizure analysis occurred at all-time points and sleep analysis occurred in week 1 and month-1/2 in all groups. Subsets of CCI and sham groups were subjected to voltageclamp experiments in hippocampal slices to evaluate GABAergic synaptic inhibition. RESULTS: DORA-22 treatment suppressed seizures in month 1-3 recordings. TBI reduced the amplitude and frequency of miniature inhibitory synaptic currents (mIPSCs) in dentate granule cells and these changes were rescued by DORA-22 treatment. Sleep analysis showed that DORA-22 increased nonrapid eye movement (NREM) sleep during lights-off whereas THIP increased REM sleep during lights-on in week 1. Both treatments displayed subtle changes in time spent in NREM or REM at month-1/2 as well. TBI not only increased normalized EEG delta power (NΔ) at week-1 and month-1 but also resulted in the loss of the homeostatic diurnal oscillation of NΔ, which was restored by DORA-22 but not THIP treatment. CONCLUSIONS: Dual orexin antagonists may have a therapeutic potential in suppressing PTE potentially by enhancing GABAergic inhibition and impacting sleep homeostatic drive.

Occlusive retinal vasculitis: novel insights into causes, pathogenesis and treatment.

PURPOSE OF REVIEW: Occlusive retinal vasculitis (ORV) has a large differential diagnosis and varied therapeutic approaches. This review highlights existing and novel causes and treatment options for ORV. RECENT FINDINGS: Mutations in CAPN5, TREX1, and TNFAIP3 have been associated with dominantly inherited forms of ORV. Various intraocular therapeutics have been shown to occasionally cause ORV; the most recent medications associated with ORV are vancomycin and brolucizumab. In cases of ORV linked to Behçet's disease, clinical trials support the use of tumor necrosis factor alpha inhibitors. SUMMARY: Identification of the underlying etiology of ORV is critical to help guide treatment. Treatment in ORV involves both treatment any underlying infection or autoimmune condition, cessation of the any offending causative agent and local treatment of neovascular complications.

Insights on synthesis and applications of graphene-based materials in wastewater treatment: A review.

Graphene has excellent unique thermal, chemical, optical, and mechanical properties such as high thermal conductivity, high chemical stability, optical transmittance, high current density, higher surface area, etc. Due to their outstanding properties, the attention towards graphene-based materials and their derivatives in wastewater treatment has been increased in recent times. Different graphene-based materials such as graphene oxides, graphene quantum dots, graphene nanoplatelets, graphene nanoribbons and other graphene-based nanocomposites are synthesized through chemical vapor deposition, mechanical and electrochemical exfoliation of graphite. In this review, the specifics about the graphenes and their derivatives, the synthesis strategy of graphene-based materials are described. This review critically explained the applications of graphene-based materials in wastewater treatment. Graphene-based materials were utilized as adsorbents, electrodes, and photocatalysts for the efficient removal of toxic pollutants such as heavy metals, dyes, pharmaceutics, antibiotics, phenols, polycyclic aromatic hydrocarbons have been highlighted and discussed. Herein, the potential scope of graphene-based material in the field of wastewater treatment is critically reviewed. In addition, a brief perspective on future research directions and difficulties in the synthesis of graphene-based material are summarized.

Masson's tumor of the ocular surface - A rare clinical entity.

Masson's tumor or intravascular papillary endothelial hyperplasia (IPEH) is a benign vascular lesion usually involving the head-and-neck region. On histopathological examination, it consists of reactive proliferation of endothelial cells with papillary formations which is the key to diagnosis. This rare entity was first described in 1923 by Pierre Masson. Lesions involving orbit and eyelids have been reported before. Here, we report a case of Masson's tumor which occurred in the lid margin and later in the conjunctiva which regressed completely after excision.

An insight into cell-laden 3D-printed constructs for bone tissue engineering.

Escalating bone graft scarcity and donor site morbidity worldwide are alarming reminders that highlight the need for alternatives to gold standard tissue rejuvenation methods. Over the last few decades, many efforts have been made in bone tissue engineering (BTE) to fabricate artificial bone transplants. Conventional BTE techniques do not render pertinent spatial organization of cells, and they fail in mimicking the extracellular matrix of native bone tissue. This setback can be overcome by using the emerging technology of three-dimensional bioprinting (3DBP). 3DBP is a state-of-the-art technology that provides accurate hierarchal biomaterial structures that accommodate live-cell patterning to mimic their native counterparts. Herein, we provide an overview on the recent progress of cell-laden 3DBP technologies and also discuss the various biomaterials utilized (natural polymers such as chitosan, collagen, gelatin, hyaluronic acid, and silk fibroin and synthetic polymers such as PCL, PVP, and ceramics) to engineer scaffolds with requisite structural, mechanical, and biological complexity. We also highlight some of the persisting challenges and the solutions to surmount them, paving the way for progress in the field. Finally, we discuss how the combination of novel modalities with 3DBP can pave the way for new frontiers, like four-dimensional bioprinting (4DBP), to bring customized, stimuli-responsive, and highly effective regenerative scaffolds to bone tissue engineering.

Polycaprolactone/polyvinylpyrrolidone coaxial electrospun fibers containing veratric acid-loaded chitosan nanoparticles for bone regeneration.

Veratric acid (3,4-dimethoxy benzoic acid) (VA) is a hydrophobic phenolic phytocompound possessing therapeutic potential, but it has not been reported as actuating bone regeneration to date. Furthermore, delivery of hydrophobic compounds is often impeded in the body, thus depreciating their bioavailability. In this study, VA was found to have osteogenic potential and its sustained delivery was facilitated through a nanoparticle-embedded coaxial electrospinning technique. Polycaprolactone/polyvinylpyrrolidone (PCL/PVP) coaxial fibers were electrospun, encasing VA-loaded chitosan nanoparticles (CHS-NP). The fibers showed commendable physiochemical and material properties and were biocompatible with mouse mesenchymal stem cells (mMSCs). When mMSCs were grown on coaxial fibers, VA promoted these cells towards osteoblast differentiation as was reflected by calcium deposits. The mRNA expression of Runx2, an important bone transcriptional regulator, and other differentiation markers such as alkaline phosphatase, collagen type I, and osteocalcin were found to be upregulated in mMSCs grown on the PCL/PVP/CHS-NP-VA fibers. Overall, the study portrays the delivery of the phytocompound, VA, in a sustained manner to promote bone regeneration.

Overexpression of Sirtuin 1 protein in neurons prevents and reverses experimental diabetic neuropathy.

In diabetic neuropathy, there is activation of axonal and sensory neuronal degeneration pathways leading to distal axonopathy. The nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylase enzyme, Sirtuin 1 (SIRT1), can prevent activation of these pathways and promote axonal regeneration. In this study, we tested whether increased expression of SIRT1 protein in sensory neurons prevents and reverses experimental diabetic neuropathy induced by a high fat diet (HFD). We generated a transgenic mouse that is inducible and overexpresses SIRT1 protein in neurons (nSIRT1OE Tg). Higher levels of SIRT1 protein were localized to cortical and hippocampal neuronal nuclei in the brain and in nuclei and cytoplasm of small to medium sized neurons in dorsal root ganglia. Wild-type and nSIRT1OE Tg mice were fed with either control diet (6.2% fat) or a HFD (36% fat) for 2 months. HFD-fed wild-type mice developed neuropathy as determined by abnormal motor and sensory nerve conduction velocity, mechanical allodynia, and loss of intraepidermal nerve fibres. In contrast, nSIRT1OE prevented a HFD-induced neuropathy despite the animals remaining hyperglycaemic. To test if nSIRT1OE would reverse HFD-induced neuropathy, nSIRT1OE was activated after mice developed peripheral neuropathy on a HFD. Two months after nSIRT1OE, we observed reversal of neuropathy and an increase in intraepidermal nerve fibre. Cultured adult dorsal root ganglion neurons from nSIRT1OE mice, maintained at high (30 mM) total glucose, showed higher basal and maximal respiratory capacity when compared to adult dorsal root ganglion neurons from wild-type mice. In dorsal root ganglion protein extracts from nSIRT1OE mice, the NAD+-consuming enzyme PARP1 was deactivated and the major deacetylated protein was identified to be an E3 protein ligase, NEDD4-1, a protein required for axonal growth, regeneration and proteostasis in neurodegenerative diseases. Our results indicate that nSIRT1OE prevents and reverses neuropathy. Increased mitochondrial respiratory capacity and NEDD4 activation was associated with increased axonal growth driven by neuronal overexpression of SIRT1. Therapies that regulate NAD+ and thereby target sirtuins may be beneficial in human diabetic sensory polyneuropathy.

Sputum Antineutrophil Cytoplasmic Antibodies in Serum Antineutrophil Cytoplasmic Antibody-Negative Eosinophilic Granulomatosis with Polyangiitis.

RATIONALE: Eosinophilic granulomatosis with polyangiitis (eGPA) is a small-vessel vasculitis where 40% of patients present with serum antineutrophil cytoplasmic antibodies (ANCAs). We examined the presence and clinical relevance of sputum ANCAs in the serum ANCA- patients with eGPA. METHODS: ANCA was investigated in matched sputum and blood samples collected from 23 patients with eGPA (n = 10, serum ANCA+), 19 patients with eosinophilic asthma (prednisone dependent), and 13 healthy volunteers. IgG reactivity to common target antigens and cytokine profiles in sputum samples were examined. Pathogenicity of detected sputum ANCA was assessed using in vitro degranulation assays. MEASUREMENTS AND MAIN RESULTS: Most patients with eGPA (17 of 23, 74%) showed significantly increased sputum ANCAs compared with patients with eosinophilic asthma (P = 0.002) and healthy controls (P < 0.0001), irrespective of their serum ANCA status. In addition, 16 of 17 (94%) of sputum ANCA+ patients had clinical manifestations of severe asthma compared with 3 of 6 (50%) in the sputum ANCA- subset (P = 0.04). Microarray analysis of 123 common antigens failed to reveal a specific target for the ANCA IgG. However, immunoprecipitated immunoglobulins from ANCA+ sputum allowed extensive extracellular trap formations from both neutrophils and eosinophils in vitro, indicating pathogenicity of detected IgG autoantibodies. Cytokine analysis showed lung-localized increases in CXCL8 (neutrophil/eosinophil chemotaxis), CCL24 (eosinophil recruitment), and CXCL12 (lymphocyte recruitment) in the sputa from ANCA+ patients (P < 0.01). CONCLUSIONS: We report a novel finding of ANCA reactivity in the sputa of patients with eGPA in whom disease severity is driven by respiratory complications. Investigating localized autoimmunity may lead to the discovery of novel pathomechanisms, therapeutic targets, and optimal biomarkers for diagnosing and managing eGPA.

Utility of prenatal Doppler ultrasound to predict neonatal impaired cerebral autoregulation.

OBJECTIVE: Determine if abnormal prenatal Doppler ultrasound indices are predictive of postnatal impaired cerebral autoregulation. STUDY DESIGN: Prospective cohort study of 46 subjects, 240-296 weeks' gestation. Utilizing near-infrared spectroscopy and receiver-operating characteristic analysis, impaired cerebral autoregulation was defined as >16.5% time spent in a dysregulated state within 96 h of life. Normal and abnormal Doppler indices were compared for perinatal outcomes. RESULTS: Subjects with abnormal cerebroplacental ratio (n = 12) and abnormal umbilical artery pulsatility index (n = 13) were likely to develop postnatal impaired cerebral autoregulation (p ≤ 0.02). Abnormal cerebroplacental ratio was associated with impaired cerebral autoregulation between 24 and 48 h of life (p = 0.016). These subjects have increased risk for fetal growth restriction, lower birth weight, lower Apgar scores, acidosis, and severe intraventricular hemorrhage and/or death (p < 0.05). CONCLUSION: Abnormal cerebroplacental ratio and umbilical artery pulsatility index are associated with postnatal impairment in cerebral autoregulation and adverse outcome.

Endogenous peroxidases in sputum interfere with horse-radish peroxidase-based ELISAs.

Peroxidase-based immunoassays are commonly used for detecting inflammatory mediators in biological samples. We suggest caution while interpreting assays particularly in sputum samples that have endogenous peroxidases like eosinophil peroxidase (EPX), which may interact with a horseradish peroxidase (HRP)-based ELISA. Using IL-8 as an example, we demonstrate that values generated with an HRP-ELISA (n=47) show significant positive correlation with the sputum EPX content (r=0.6, P=0.0004), which can be misconstrued to be affiliated with an eosinophilic event. The data-set generated with the same samples (n=47) using alkaline phosphatase (AP)-based ELISA and a non-enzymatic Milliplex system do not show any correlation with sputum EPX (Milliplex r=-0.24, P=0.13; AP r=0.26, P=0.09). Moreover, sub-group analysis shows significantly increased IL-8 levels detected by HRP-ELISA in eosinophilic patient sputa (n=28) compared to AP-ELISA (P=0.0001). We, therefore, recommend the use of AP-based ELISA or Multiplex system rather than peroxidase-based ELISA for detecting soluble mediators, and more importantly for non-Th2 related mediators in sputum samples with increased eosinophil activity.

An overview of frenal attachments.

Frenal attachments are thin folds of mucous membrane with enclosed muscle fibers that attach the lips to the alveolar mucosa and underlying periosteum. Most often, during the oral examination of the patient the dentist gives very little importance to the frenum, for assessing its morpholology and attachment. However, it has been seen that an abnormal frenum can be an indicator of a syndrome. This paper highlights the different frenal attachments seen in association with various syndromic as well as non-syndromic conditions.