Punctate Inner Choroidopathy (PIC) disease recurrence with inflammatory choroidal neovascular membrane (iCNVM) post-COVID-19 vaccine.

PURPOSE: To report a recurrence of punctate inner choroidopathy (PIC) with an inflammatory choroidal neovascular membrane (iCNVM) after the Pfizer-BioNTech COVID-19 vaccine. METHODS: Case report. RESULTS: A 38-year-old female with a history of myopia and previous episodes of PIC and iCNVM presented with distorted vision in her right eye, seven days after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine. The patient exhibited active PIC lesions with iCNVM confirmed on multimodal imaging. Treatment with a combination of oral corticosteroids and intravitreal anti-VEGF injection led to disease resolution. Subsequent COVID-19 vaccinations, administered while the patient was immunosuppressed, did not lead to disease relapse. However, relapse occurred following the fourth COVID-19 vaccine, when the patient was not immune suppressed. CONCLUSION: This case highlights the potential risk of PIC disease relapse following COVID-19 vaccination. Further research is needed to investigate the relationship between COVID-19 vaccination and PIC exacerbation, as well as to determine optimal management strategies in this population, including close observation and consideration of prophylactic immune suppression at the time of COVID-19 vaccine for high-risk individuals.

Erratum: 541 A Framework for Multicultural and Multidisciplinary Near-Peer Mentoring for Artificial Intelligence in Healthcare Education: A University of Florida Friend Group - CORRIGENDUM.

[This corrects the article DOI: 10.1017/cts.2024.462.].

Recent advances in green synthesized nanoparticles for bactericidal and wound healing applications.

Nanotechnology has become an exciting area of research in diverse fields, such as: healthcare, food, agriculture, cosmetics, paints, lubricants, fuel additives and other fields. This review is a novel effort to update the practioneers about the most current developments in the widespread use of green synthesized nanoparticles in medicine. Biosynthesis is widely preferred among different modes of nanoparticle synthesis since they do not require toxic chemical usage and they are environment-friendly. In the green bioprocess, plant, algal, fungal and cyanobacterial extract solutions have been utilized as nucleation/capping agents to develop effective nanomaterials for advanced medical applications. Several metal salts, such as silver, zinc, titanium and other inorganic salts, were utilized to fabricate innovative nanoparticles for healthcare applications. Irrespective of the type of wound, infection in the wound area is a widespread problem. Micro-organisms, the prime reason for wound complications, are gradually gaining resistance against the commonly used antimicrobial drugs. This necessitates the need to generate nanoparticles with efficient antimicrobial potential to keep the pathogenic microbes under control. These nanoparticles can be topically applied as an ointment and also be used by incorporating them into hydrogels, sponges or electrospun nanofibers. The main aim of this review is to highlight the recent advances in the Ag, ZnO and TiO2 nanoparticles with possible wound healing applications, coupled with the bactericidal ability of a green synthesis process.

Juvenile otosclerosis and congenital stapes footplate fixation. A systematic review and meta-analysis of surgical outcomes and management.

OBJECTIVE: Juvenile Otosclerosis (JO) and Congenital Stapes Footplate Fixation (CSFF) are rare ossicular chain disorders seen in the paediatric population and present with conductive hearing loss. Ongoing controversy exists regarding the role of surgical intervention in JO and CSFF given the poorer hearing outcomes and complications when compared with surgical intervention for adult otosclerosis. The objective of this study is to assess the published data on the surgical outcomes of JO and CSFF in order to guide clinicians and counsel patients on the various medical options for these disease entities. METHODS: A systematic review of MEDLINE, EMBASE and Cochrane was performed with inclusion criteria of children with JO or CSFF and hearing outcomes following stapes surgery. Studies identified by the search were reviewed and assessed by two independent reviewers in line with the PRISMA guidelines. RESULTS: 464 articles were initially reviewed and 28 articles met inclusion in the systematic review and meta-analysis. A total of 810 ears (473 and 337 cases of JO and CSFF respectively) underwent stapes surgery. Average age at time of surgery for JO and CSFF was 14.3 and 10.2 years old respectively. The mean pre-operative Air-Bone-Gap (ABG) for JO and CSFF was 31.8 ± 5.2 dB and 39.4 ± 10 dB respectively. Following stapes surgery, the mean post-operative ABG for JO and CSFF was 9.6 ± 6 dB and 19.2 ± 12.5 dB respectively. Surgical success rate (defined as ABG <10 dB) was 81% for JO and 41% for CSFF. Mean ABG gain for JO and CSFF was 24.8 dB (95% CI: 18.6-33.1) and 22.6 dB (95% CI: 18.4-27.8) respectively. The reported number of dead ears was 4/473 (0.8%) for JO and 2/337 (0.6%) for CSFF. 23 cases (2.8%) reported sensorineural hearing loss (SNHL) >10 dB. CONCLUSION: CSFF was associated with poorer hearing outcomes compared to JO, however both entities showed similar improvement in ABG post operatively. Counselling patients and their families on the surgical success rates and complications of JO or CSFF is an important part of the decision making process when deciding between a surgical option or conservative measures such as hearing aids.

HIV-Positive Patients on Antiretroviral Therapy Have an Altered Mucosal Intestinal but Not Oral Microbiome.

This study characterized compositional and functional shifts in the intestinal and oral microbiome in HIV-positive patients on antiretroviral therapy compared to HIV-negative individuals. Seventy-nine specimens were collected from 5 HIV-positive and 12 control subjects from five locations (colon brush, colon wash, terminal ileum [TI] brush, TI wash, and saliva) during colonoscopy and at patient visits. Microbiome composition was characterized using 16S rRNA sequencing, and microbiome function was predicted using bioinformatics tools (PICRUSt and BugBase). Our analysis indicated that the ß-diversity of all intestinal samples (colon brush, colon wash, TI brush, and TI wash) from patients with HIV was significantly different from patients without HIV. Specifically, bacteria from genera Prevotella, Fusobacterium, and Megasphaera were more abundant in samples from HIV-positive patients. On the other hand, bacteria from genera Ruminococcus, Blautia, and Clostridium were more abundant in samples from HIV-negative patients. Additionally, HIV-positive patients had higher abundances of biofilm-forming and pathogenic bacteria. Furthermore, pathways related to translation and nucleotide metabolism were elevated in HIV-positive patients, whereas pathways related to lipid and carbohydrate metabolism were positively correlated with samples from HIV-negative patients. Our analyses further showed variations in microbiome composition in HIV-positive and negative patients by sampling site. Samples from colon wash, colon brush, and TI wash were significant between groups, while samples from TI brush and saliva were not significant. Taken together, here, we report altered intestinal microbiome composition and predicted function in patients with HIV compared to uninfected patients, though we found no changes in the oral microbiome. IMPORTANCE Over 37 million people worldwide are living with HIV. Although the availability of antiretroviral therapy has significantly reduced the number of AIDS-related deaths, individuals living with HIV are at increased risk for opportunistic infections. We now know that HIV interacts with the trillions of bacteria, fungi, and viruses in the human body termed the microbiome. Only a limited number of previous studies have compared variations in the oral and gastrointestinal microbiome with HIV infection. Here, we detail how the oral and gastrointestinal microbiome changes with HIV infection, having used 5 different sampling sites to gain a more comprehensive view of these changes by location. Our results show site-specific changes in the intestinal microbiome associated with HIV infection. Additionally, we show that while there were significant changes in the intestinal microbiome, there were no significant changes in the oral microbiome.

Structural foundations for explaining the physiological roles of murzymes embedded in diverse phospholipid membranes.

The advent of improved structural biology protocols and bioinformatics methodologies have provided paradigm-shifting insights on metabolic or physiological processes catalyzed by homo-/hetero- proteins (super)complexes embedded in phospholipid membranes of cells/organelles. In this panoramic review, we succinctly elucidate the structural features of select redox proteins from four systems: hepatocyte/adrenal cortex endoplasmic reticulum (microsomes), inner mitochondrial membrane (cristae), thylakoid membrane (grana), and in the flattened disks of rod/cone cells (in retina). Besides catalyzing fast/crucial (photo)chemical reactions, these proteins utilize the redox-active diatomic gaseous molecule of oxygen, the elixir of aerobic life. Quite contrary to extant perceptions that invoke primarily deterministic affinity-binding or conformation-change based "proton-pump"/"serial electron-relay" type roles, we advocate murzyme functions for the membrane-embedded proteins in these systems. Murzymes are proteins that generate/stabilize/utilize diffusible reactive (oxygen) species (DRS/DROS) based activities. Herein, we present a brief compendium of the recently revealed wealth of structural information and mechanistic concepts on how the membrane proteins use DRS/DROS to aid 'effective charge separation' and facilitate trans-membrane dynamics of diverse species in milieu, thereby enabling the cells to function as 'simple chemical engines'.

No interface energy barrier and increased surface pinning in low temperature baked niobium.

Superconducting Radio-Frequency cavities are currently made out of niobium. Niobium cavities are limited by the magnetic field on the cavity walls due to the entry of vortices at the field of first vortex penetration, H[Formula: see text]. Low temperature baking in vacuum or low pressure gas atmosphere removes the strong decrease of the quality factor with accelerating gradient (high field Q-slope). Some cavities reach surface magnetic field above the lower critical field H[Formula: see text]. One hypothesis for this performance increase is that the outer layer affected by the treatments acts as a barrier for vortex penetration (effective bilayer). Using a vibrating sample magnetometer the field of first flux penetration (H[Formula: see text]) was measured for Nb ellipsoids with various low temperature treatments. All H[Formula: see text] values were found to be consistent with the lower critical field, H[Formula: see text], as predicted for clean niobium. This led to the conclusion that a metastable flux free state above H[Formula: see text] cannot be observed in DC magnetometry for low temperature baked niobium unlike for bilayers consisting of two superconductors as previously published. The effect of flux pinning differed significantly between treatments, suggesting that the high field Q-slope mitigation might be related to vortex pinning in the surface of the cavities.

Interaction of membrane-embedded cytochrome b-complexes with quinols: Classical Q-cycle and murburn model.

We recently proposed a diffusible reactive (oxygen) species (DRS/DROS) based function for cytochrome b complexes (CBC) and quinones (Q)/quinols (QH2 ) in the murburn model of bioenergetics. This proposal is in direct conflict with the classical purview of Q-cycle. Via extensive analyses of the structure-function correlations of membrane-quinones/quinols and proteins, we present qualitative and quantitative arguments to infer that the classical model cannot explain the energetics, kinetics, mechanism and probabilistic considerations. Therefore, it is proposed that Q-cycle is neither necessary nor feasible at CBCs. In contrast, we substantiate that the murburn model explains: (a) crucial structural data of CBCs, (b) why quinones/quinols are utilized in bioenergetic membranes, (c) how trans-membrane potential is generated owing to effective charge separation at CBCs, (d) mobility data of O2 , DRS, Q/QH2 , and (e) utility of other reaction/membrane components. Further, the murburn model also accommodates the absence of quinones in anaerobic Archaea, wherein methanophenazines are prevalent. The work mandates that the textbooks and research agendas are refreshed to reflect the new perception. SIGNIFICANCE: The current article must be seen as a critical and detailed analysis of the role and working mechanism of quinone (Q) /quinols (QH2 ) in bioenergetic membranes. In the classical model, QH2 are perceived as highly mobile electron-transport agents that bind and donate electrons to cytochrome b complexes (CBCs), using sophisticated electronic circuitries, in order to recycle Q and pump protons. The classical perception sees radicals (such as Q*-, O2 *-, etc., also called diffusible reactive species, DRS) as wasteful or toxic (patho) physiological manifestations. It is highlighted herein that QH2 has low mobility and matrix has little protons to pump. New insights from the structural analyses of diverse CBCs and quinols, in conjunction with murburn reaction thermodynamics suggest that the electrons from substrates/quinols are effectively utilized via DRS. This perception fits into a much broader analysis of 1 and 2 electron transfers in overall redox metabolism, as recently brought out by the murburn model, wherein DRS are considered obligatory ingredients of physiology. Thus, the findings mandate a reorientation in the pertinent research field.

Are plastocyanin and ferredoxin specific electron carriers or generic redox capacitors? Classical and murburn perspectives on two photosynthetic proteins.

In the light reaction of oxygenic photosynthesis, plastocyanin (PC) and ferredoxins (Fd) are small/diffusible redox-active proteins playing key roles in electron transfer/transport phenomena. In the Z-scheme mechanistic purview, they are considered as specific affinity binding-based electron-relay agents, linking the functions of Cytochrome b6f (Cyt. b6f), Photosystem I (PS I) and Fd:NADPH oxidoreductase (FNR). The murburn explanation for photolytic photophosphorylation deems PC/Fd as generic 'redox capacitors', temporally accepting and releasing one-electron equivalents in reaction milieu. Herein, we explore the two theories with respect to structural, distributional and functional aspects of PC/Fd. Amino acid residues located on the surface loci of key patches of PC/Fd vary in electrostatic/contour (topography) signatures. Crystal structures of four different complexes each of Cyt.f-PC and Fd-FNR show little conservation in the contact-surfaces, thereby discrediting 'affinity binding-based electron transfers (ET)' as an evolutionary logic. Further, thermodynamic and kinetic data of wildtype and mutant proteins interactions do not align with Z-scheme. Furthermore, micromolar physiological concentrations of PC and the non-conducive architecture of chloroplasts render the classical model untenable. In the murburn model, as PC is optional, the observation that plants lacking PC survive and grow is justified. Further, the low physiological concentration/distribution of PC in chloroplast lumen/stroma is supported by murburn equilibriums, as higher concentrations would limit electron transfers. Thus, structural evidence, interactive dynamics with redox partners and physiological distribution/role of PC/Fd support the murburn perspective that these proteins serve as generic redox-capacitors in chloroplasts.Communicated by Ramaswamy H. Sarma.

Hemoglobin catalyzes ATP-synthesis in human erythrocytes: a murburn model.

Blood hemoglobin (Hb), known to transport oxygen, is the most abundant globular protein in humans. Erythrocytes have ∼10-3 M concentration of ATP in steady-state and we estimate that this high amounts cannot be formed from 10-4 - 10-7 M levels of precursors via substrate-level phosphorylation of glycolysis. To account for this discrepancy, we propose that Hb serves as a 'murzyme' (a redox enzyme working along the principles of murburn concept), catalyzing the synthesis of the major amounts of ATP found in erythrocytes. This proposal is along the lines of our earlier works demonstrating DROS (diffusible reactive oxygen species) mediated ATP-synthesis as a thermodynamically and kinetically viable mechanism for physiological oxidative phosphorylation. We support the new hypothesis for Hb with theoretical arguments, experimental findings of reputed peers and in silico explorations. Using in silico methods, we demonstrate that adenosine nucleotide and 2,3-bisphosphoglycerate (2,3-BPG) binding sites are located suitably on the monomer/tetramer, thereby availing facile access to the superoxide emanating from the heme center. Our proposal explains earlier reported in situ experimental findings/suggestions of 2,3-BPG and ADP binding at the same locus on Hb. The binding energy is in the order of 2,3-BPG > NADH > ATP > ADP > AMP and agrees with earlier reports, potentially explaining the bioenergetic physiology of erythrocytes. Also, the newly discovered site for 2,3-BPG shows lower affinity in fetal Hb (as compared to adults) explaining oxygen transfer from mother to embryo. The findings pose significant implications in routine physiology and pathologies like sickle cell anemia and thalassemia.Communicated by Ramaswamy H. Sarma.

Mechanism of electron transfers mediated by cytochromes c and b5 in mitochondria and endoplasmic reticulum: classical and murburn perspectives.

We explore the mechanism of electron transfers mediated by cytochrome c, a soluble protein involved in mitochondrial oxidative phosphorylation and cytochrome b5, a microsomal membrane protein acting as a redox aide in xenobiotic metabolism. We found minimal conservation in the sequence and surface amino acid residues of cytochrome c/b5 proteins among divergent species. Therefore, we question the evolutionary logic for electron transfer (ET) occurring through affinity binding via recognition of specific surface residues/topography. Also, analysis of putative protein-protein interactions in the crystal structures of these proteins and their redox partners did not point to any specific interaction logic. A comparison of the kinetic and thermodynamic constants of wildtype vs. mutants did not provide strong evidence to support the binding-based ET paradigm, but indicated support for diffusible reactive species (DRS)-mediated process. Topographically divergent cytochromes from one species have been substituted for reaction with proteins from other species, implying the involvement of non-specific interactions. We provide a viable alternative (murburn concept) to classical protein-protein binding-based long range ET mechanism. To account for the promiscuity of interactions and solvent-accessible hemes, we propose that the two proteins act as non- specific redox capacitors, mediating one-electron redox equilibriums involving DRS and unbound ions.Communicated by Ramaswamy H. Sarma.

Structure-function correlations and system dynamics in oxygenic photosynthesis: classical perspectives and murburn precepts.

HIGHLIGHTS: Contemporary beliefs on oxygenic photosynthesis are critiqued.Murburn model is suggested as an alternative explanation.In the new model, diffusible reactive species are the main protagonists.All pigments are deemed photo-redox active in the new stochastic mechanism.NADPH synthesis occurs via simple electron transfers, not via elaborate ETC.Oxygenesis is delocalized and not just centered at Mn-Complex.Energetics of murburn proposal for photophosphorylation is provided.The proposal ushers in a paradigm shift in photosynthesis research.

Validating the predictions of murburn model for oxygenic photosynthesis: Analyses of ligand-binding to protein complexes and cross-system comparisons.

In this second half of our treatise on oxygenic photosynthesis, we provide support for the murburn model of the light reaction of photosynthesis and ratify key predictions made in the first part. Molecular docking and visualization of various ligands of quinones/quinols (and their derivatives) with PS II/Cytochrome b6f complexes did not support chartered 2e-transport role of quinols. A broad variety of herbicides did not show any affinity/binding-based rationales for inhibition of photosynthesis. We substantiate the proposal that disubstituted phenolics (perceived as protonophores/uncouplers or affinity-based inhibitors in the classical purview) serve as interfacial modulators of diffusible reactive (oxygen) species or DR(O)S. The DRS-based murburn model is evidenced by the identification of multiple ADP-binding sites on the extra-membraneous projection of protein complexes and structure/distribution of the photo/redox catalysts. With a panoramic comparison of the redox metabolic machinery across diverse organellar/cellular systems, we highlight the ubiquitous one-electron murburn facets (cofactors of porphyrin, flavin, FeS, other metal centers and photo/redox active pigments) that enable a facile harnessing of the utility of DRS. In the summative analyses, it is demonstrated that the murburn model of light reaction explains the structures of membrane supercomplexes recently observed in thylakoids and also accounts for several photodynamic experimental observations and evolutionary considerations. In toto, the work provides a new orientation and impetus to photosynthesis research. Communicated by Ramaswamy H. Sarma.

Murburn precepts for lactic-acidosis, Cori cycle, and Warburg effect: Interactive dynamics of dehydrogenases, protons, and oxygen.

It is unresolved why lactate is transported to the liver for further utilization within the physiological purview of Cori cycle, when muscles have more lactate dehydrogenase (LDH) than liver. We point out that the answer lies in thermodynamics/equilibriums. While the utilization of NADH for the reduction of pyruvate to lactate can be mediated via the classical mechanism, the oxidation of lactate (with/without the uphill reduction of NAD+ ) necessitates alternative physiological approaches. The latter pathway occurs via interactive equilibriums involving the enzyme, protons and oxygen or diffusible reactive oxygen species (DROS). Since liver has high DROS, the murburn activity at LDH would enable the cellular system to tide over the unfavorable energy barriers of the forward reaction (~476 kJ/mol; earlier miscalculated as ~26 kJ/mole). Further, the new mechanism does not necessitate any "smart decision-making" or sophisticated control by/of proteins. The DROS-based murburn theory explains the invariant active-site structure of LDH isozymes and their multimeric nature. The theoretical insights, in silico evidence and analyses of literature herein also enrich our understanding of the underpinnings of "lactic acidosis" (lowering of physiological pH accompanied by lactate production), Warburg effect (increased lactate production at high pO2 by cancer cells) and approach for cancer therapy.

Why do cells need oxygen? Insights from mitochondrial composition and function.

Mitochondrial membrane-embedded redox proteins are classically perceived as deterministic "electron transport chain" (ETC) arrays cum proton pumps; and oxygen is seen as an "immobile terminal electron acceptor." This is untenable because: (1) there are little free protons to be pumped out of the matrix; (2) proton pumping would be highly endergonic; (3) ETC-chemiosmosis-rotary ATP synthesis proposal is "irreducibly complex"/"non-evolvable" and does not fit with mitochondrial architecture or structural/distribution data of the concerned proteins/components; (4) a plethora of experimental observations do not conform to the postulates/requisites; for example, there is little evidence for viable proton-pumps/pH-gradient in mitochondria, trans-membrane potential (TMP) is non-fluctuating/non-trappable, oxygen is seen to give copious "diffusible reactive (oxygen) species" (DRS/DROS) in milieu, etc. Quite contrarily, the newly proposed murburn model's tenets agree with known principles of energetics/kinetics, and builds on established structural data and reported observations. In this purview, oxygen is needed to make DRS, the principal component of mitochondrial function. Complex V and porins respectively serve as proton-inlet and turgor-based water-exodus portals, thereby achieving organellar homeostasis. Complexes I to IV possess ADP-binding sites and their redox-centers react/interact with O2 /DRS. At/around these complexes, DRS cross-react or activate/oxidize ADP/Pi via fast thermogenic one-electron reaction(s), condensing to form two-electron stabilized products (H2 O2 /H2 O/ATP). The varied architecture and distribution of components in mitochondria validate DRS as (i) the coupling agent of oxidative reactions and phosphorylations, and (ii) the primary reason for manifestation of TMP in steady-state. Explorations along the new precepts stand to provide greater insights on mitochondrial function and pathophysiology.

Spotlight on Asteroid Hyalosis: A Clinical Perspective.

Asteroid hyalosis is a benign degenerative condition of the vitreous that is often asymptomatic. Our purpose with this narrative review is to provide a current overview of asteroid hyalosis from a clinical perspective. We review the epidemiology and risk factors, the clinical diagnosis and differential diagnoses, clinical challenges in eyes with asteroid hyalosis, and the treatment of asteroid hyalosis. Many clinical questions remain unanswered, and the current evidence to guide clinical practice is largely based on anecdotal evidence and clinical experience. More studies on asteroid hyalosis from a clinical perspective are warranted.

What is the Role of Lipid Membrane-embedded Quinones in Mitochondria and Chloroplasts? Chemiosmotic Q-cycle versus Murburn Reaction Perspective.

Quinones are found in the lipid membranes of prokaryotes like E. coli and cyanobacteria, and are also abundant in eukaryotic mitochondria and chloroplasts. They are intricately involved in the reaction mechanism of redox phosphorylations. In the Mitchellian chemiosmotic school of thought, membrane-lodged quinones are perceived as highly mobile conveyors of two-electron equivalents from the first leg of Electron Transport Chain (ETC) to the 'second pit-stop' of Cytochrome bc1 or b6f complex (CBC), where they undergo a regenerative 'Q-cycle'. In Manoj's murburn mechanism, the membrane-lodged quinones are perceived as relatively slow-moving one- or two- electron donors/acceptors, enabling charge separation and the CBC resets a one-electron paradigm via 'turbo logic'. Herein, we compare various purviews of the two mechanistic schools with respect to: constraints in mobility, protons' availability, binding of quinones with proteins, structural features of the protein complexes, energetics of reaction, overall reaction logic, etc. From various perspectives, the murburn mechanism appeals as a viable alternative explanation well-rooted in thermodynamics/kinetics and one which lends adequate structure-function correlations for the roles of quinones, lipid membrane and associated proteins.