Subfoveal neurosensory detachment flattening and observe (SNF-Ob) approach for the management of Ci-DMO - a multicentric study.

PURPOSE: To understand subfoveal neurosensory detachment flattening and observe (SNF-Ob) strategy and its relationship with visual acuity in the management of centre-involved diabetic macular oedema (Ci-DMO). METHODS: This was a multicentric retrospective observational study. We reviewed data of 188 eyes of 130 patients who presented with Ci-DMO with subfoveal neurosensory detachment (NSD) and treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents or steroids. The primary outcome was best corrected visual acuity (BCVA) measured at the time of the first subfoveal neurosensory detachment flattening (SNF) and at the end of follow-up. RESULTS: Eyes that achieved 20/50 (LogMAR = 0.40) or better at first SNF had mean LogMAR BCVA 0.38 ± 0.21, 0.24 ± 0.11 and 0.21 ± 0.15 at baseline, at the time of first SNF, and at the end of the last follow-up respectively. Mean LogMAR BCVA significantly improved from baseline to first SNF (p < 0.0001; 95% CI 0.115-0.183) and at the end of the last follow-up (p < 0.0001; 95% CI 0.126-0.213) with a change of Early Treatment Diabetic Retinopathy Study (ETDRS) 10 letters. There was no significant difference in improvement in BCVA from the first SNF and at the end of the last follow-up (p = 0.0781; 95% CI -0.002 to 0.046). CONCLUSIONS: Eyes presenting with Ci-DMO and subfoveal NSD are unlikely to improve at SNF with BCVA > 20/50 (LogMAR = 0.40). Further evidence is needed before the combination of good BCVA and SNF may be considered as endpoint of pharmacological therapy for DMO.

Acute ocular hypertension in the living human eye: Model description and initial cellular responses to elevated intraocular pressure.

This initial methods study presents the initial immunohistochemical and transcriptomic changes in the optic nerve head and retina from three research-consented brain-dead organ donors following prolonged and transient intraocular pressure (IOP) elevation. In this initial study, research-consented brain-dead organ donors were exposed to unilateral elevation of IOP for 7.5 h (Donor 1), 30 h (Donor 2), and 1 h (Donor 3) prior to organ procurement. Optic nerve tissue and retinal tissue was obtained following organ procurement for immunohistological and transcriptomic analysis. Optic nerve sections in Donor 1 exposed to 7.5-hours of unilateral sub-ischemic IOP elevation demonstrated higher levels of protein expression of the astrocytic marker, glial fibrillary acidic protein (GFAP), within the lamina cribrosa with greatest expression inferior temporally in the treated eye compared to control. Spatial transcriptomic analysis performed on optic nerve head tissues from Donor 2 exposed to 30 h of unilateral IOP elevation demonstrated differential transcription of mRNA across laminar and scleral regions. Immunohistochemistry of retinal sections from Donor 2 exhibited higher GFAP and IBA1 expression in the treated eye compared with control, but this was not observed in Donor 3, which was exposed to only 1-hour of IOP elevation. While there were no differences in GFAP protein expression in the retina following the 1-hour IOP elevation in Donor 3, there were higher levels of transcription of GFAP in the inner nuclear layer, and CD44 in the retinal ganglion cell layer, indicative of astrocytic and Müller glial reactivity as well as an early inflammatory response, respectively. We found that transcriptomic differences can be observed across treated and control eyes following unilateral elevation of IOP in brain dead organ donors. The continued development of this model affords the unique opportunity to define the acute mechanotranscriptomic response of the optic nerve head, evaluate the injury and repair mechanisms in the retina in response to IOP elevation, and enable correlation of in vivo imaging and functional testing with ex vivo cellular responses for the first time in the living human eye.

Case Report and Review of the Literature: Ischemic Stroke in Dengue Virus Infection.

Dengue continues to pose a global health challenge, particularly in tropical and subtropical areas. Dengue can impact various organs, including the central nervous system, and can cause various neurological symptoms, although stroke is an uncommon complication. Among strokes, ischemic stroke is very uncommon in dengue. A 27-year-old unmarried female was referred to our institution with 8 days of fever and myalgia, 5 days of vomiting, and 3 days of altered sensorium. Small-sized bilateral pupils reacted slowly to light. Chest auscultation revealed diffuse coarse crepitation. Poor general condition and labored breathing led to intensive care unit transfer and intubation. Her contrast-enhanced brain magnetic resonance image showed chronic pontine infarction. She was diagnosed with dengue fever (NS1Ag positive) complicated by bilateral pontine infarction. After a long course of illness, she was finally discharged to home in good recovery status. Clinicians need to be aware of the uncommon dengue presentation of stroke. Treatment is supportive with variable outcomes.

Molecular heterogeneity of quiescent melanocyte stem cells revealed by single-cell RNA-sequencing.

Melanocyte stem cells (McSCs) of the hair follicle are a rare cell population within the skin and are notably underrepresented in whole-skin, single-cell RNA sequencing (scRNA-seq) datasets. Using a cell enrichment strategy to isolate KIT+/CD45- cells from the telogen skin of adult female C57BL/6J mice, we evaluated the transcriptional landscape of quiescent McSCs (qMcSCs) at high resolution. Through this evaluation, we confirmed existing molecular signatures for qMcCS subpopulations (e.g., Kit+, Cd34+/-, Plp1+, Cd274+/-, Thy1+, Cdh3+/-) and identified novel qMcSC subpopulations, including two that differentially regulate their immune privilege status. Within qMcSC subpopulations, we also predicted melanocyte differentiation potential, neural crest potential, and quiescence depth. Taken together, the results demonstrate that the qMcSC population is heterogeneous and future studies focused on investigating changes in qMcSCs should consider changes in subpopulation composition.

Excitons, optical spectra, and electronic properties of semiconducting Hf-based MXenes.

Semiconducting MXenes are an intriguing two-dimensional (2D) material class with promising electronic and optoelectronic properties. Here, we focused on recently prepared Hf-based MXenes, namely, Hf3C2O2 and Hf2CO2. Using the first-principles calculation and excited state corrections, we proved their dynamical stability, reconciled their semiconducting behavior, and obtained fundamental gaps by using the many-body GW method (indirect 1.1 and 2.2 eV; direct 1.4 and 3.5 eV). Using the Bethe-Salpeter equation, we subsequently provided optical gaps (0.9 and 2.7 eV, respectively), exciton binding energies, absorption spectra, and other properties of excitons in both Hf-based MXenes. The indirect character of both 2D materials further allowed for a significant decrease of excitation energies by considering indirect excitons with exciton momentum along the Γ-M path in the Brillouin zone. The first bright excitons are strongly delocalized in real space while contributed by only a limited number of electron-hole pairs around the M point in the k-space from the valence and conduction band. A diverse range of excitonic states in Hf3C2O2 MXene lead to a 4% and 13% absorptance for the first and second peaks in the infrared region of absorption spectra, respectively. In contrast, a prominent 28% absorptance peak in the visible region appears in Hf2CO2 MXene. Results from radiative lifetime calculations indicate the promising potential of these materials in optoelectric devices requiring sustained and efficient exciton behavior.

Global experience of faricimab in clinical settings - a review.

INTRODUCTION: Faricimab is a bispecific antibody that acts to reduce neoangiogenesis in exudative retinal vascular disorders. It is approved for use in neovascular age-related macular degeneration and diabetic macular edema. We review the published efficacy and safety of faricimab in clinical settings. AREAS COVERED: A comprehensive literature review was conducted. Based on the 14 published real-world studies, 1127 patients (1204 eyes) were treated with faricimab. The majority of studies (14) included pre-treated patients. Most studies (13) showed central macular thickness improvement. However visual acuity improved in only half of the studies analyzed. Four studies demonstrated an extension of the treatment. Only 4 eyes (0.33%) reported intraocular inflammation and 3 eyes (0.24%) reported retinal pigment epithelial tear. EXPERT OPINION: The clinical experience with faricimab to date has the potential to provide a stable visual outcome with reduced treatment burden in cases that are resistant to other approved anti-VEGF agents. There are no major safety concerns based on this data analysis.

Digital Gangrene Associated with Scrub Typhus: A Case Series.

Rickettsial diseases cover a broad spectrum of illnesses. Scrub typhus is present worldwide, and Orientia tsutsugamushi is the causative agent of this chigger mite-borne infectious illness. Infections exhibit a range of severity, from mild illness to the more severe manifestation of multiorgan failure. We report three cases of scrub fever (55-year-old female, 63-year-old female, and 29-year-old male), all cases developed focal or pan-digital gangrene. All cases were successfully treated by administering doxycycline and additional supportive measures. Digital gangrene is uncommon in scrub typhus. Clinical suspension for early diagnosis and appropriate treatment may avoid further complications.

Spontaneous Intracranial Hemorrhage and Acute Respiratory Distress Syndrome Associated with Dengue: A Case Report.

BACKGROUND: Dengue is a major health burden worldwide, notably in tropical and subtropical countries, with symptoms ranging from asymptomatic infection to severe hemorrhagic or shock syndrome. The clinical and biochemical profile of dengue has been shown in the literature to be expanding as more atypical signs have been added over the past few decades. Most dengue-related symptoms are typically mild to moderate and self-limited. However, intracranial hemorrhage and acute respiratory distress syndrome in severe dengue is an event that has been encountered uncommonly. CASE PRESENTATION: A 30-year-old female presented with complaints of fever, headache, cough, and altered sensorium. Later, she was diagnosed with severe dengue fever complicated by dengue hemorrhagic fever, which manifested as subarachnoid and subdural bleeding and acute respiratory distress syndrome. She was managed conservatively with a positive outcome. CONCLUSION: Atypical manifestation, though rare, should be kept in mind while dealing with severe dengue patients, as early detection based on anticipated risk factors and timely treatment have the potential to save lives.

NK and NKT cells in the pathogenesis of Hidradenitis suppurativa: Novel therapeutic strategy through targeting of CD2.

Hidradenitis suppurativa (HS) is a chronic debilitating inflammatory skin disease with poorly understood pathogenesis. Single-cell RNAseq analysis of HS lesional and healthy individual skins revealed that NKT and NK cell populations were greatly expanded in HS, and they expressed elevated CD2, an activation receptor. Immunohistochemistry analyses confirmed significantly expanded numbers of CD2+ cells distributed throughout HS lesional tissue, and many co-expressed the NK marker, CD56. While CD4+ T cells were expanded in HS, CD8 T cells were rare. CD20+ B cells in HS were localized within tertiary follicle like structures. Immunofluorescence microscopy showed that NK cells (CD2 + CD56 dim ) expressing perforin, granzymes A and B were enriched within the hyperplastic follicular epidermis and tunnels of HS and juxtaposed with apoptotic cells. In contrast, NKT cells (CD2 + CD3 + CD56 bright ) primarily expressed granzyme A and were associated with α-SMA expressing fibroblasts within the fibrotic regions of the hypodermis. Keratinocytes and fibroblasts expressed high levels of CD58 (CD2 ligand) and they interacted with CD2 expressing NKT and NK cells. The NKT/NK maturation and activating cytokines, IL-12, IL-15 and IL-18, were significantly elevated in HS. Inhibition of cognate CD2-CD58 interaction with blocking anti-CD2 mAb in HS skin organotypic cultures resulted in a profound reduction of the inflammatory gene signature and secretion of inflammatory cytokines and chemokines in the culture supernate. In summary, we show that a cellular network of heterogenous NKT and NK cell populations drives inflammation, tunnel formation and fibrosis in the pathogenesis of HS. Furthermore, CD2 blockade is a viable immunotherapeutic approach for the management of HS.

Knowledge, attitude, and practice patterns of Indian ophthalmologists regarding medicolegal issues.

PURPOSE: To assess the knowledge, attitude, and practice patterns (KAPP) of Indian ophthalmologists regarding medicolegal issues using an initial survey. METHODS: An online form was circulated among Indian ophthalmologists of all ages over social media and email by the Young Ophthalmologists Society of India (YOSI) and its medicolegal working group. Anonymous responses were obtained and analyzed for each question. The questionnaire comprised questions about demographic details, KAPP of medicolegal issues including how to deal with medicolegal issues (if faced), medical indemnity insurance, deviation from the recommended minimum sum assured (Rs. 1 crore for Indian ophthalmologists), and legal service providers. RESULTS: A total of 109 responses were obtained. The majority of the respondents were male (60, 55%). More than 50% of respondents (58, 53.2%) were younger than 35 years. More than one-fourth of the respondents were private practitioners (29, 27%), and the majority were of senior consultant designation (45, 41%). Around 80% of respondents (89, 81.6%) were aware of professional indemnity insurance; however, only 54% (n = 59) bought the insurance cover. A majority of the respondents (38, 64.4%) had an indemnity cover of a maximum of Rs. 50 lacs. Only 20% of respondents were aware of the expert body at the state/national level that deals with medicolegal cases. Thirty percent of respondents recommended the ideal cover amount to be more than Rs. 1 crore. CONCLUSION: The current survey highlights the dismally low rate of awareness of medicolegal issues among ophthalmologists. Specifically, a majority of Indian ophthalmologists surveyed did not have recommended minimum insured cover for professional indemnity insurance. Larger studies are needed to further explore KAPP of Indian ophthalmologists in various medicolegal issues.

Integrated Systems Biology Pipeline to Compare Co-Expression Networks in Plants and Elucidate Differential Regulators.

To identify sets of genes that exhibit similar expression characteristics, co-expression networks were constructed from transcriptome datasets that were obtained from plant samples at various stages of growth and development or treated with diverse biotic, abiotic, and other environmental stresses. In addition, co-expression network analysis can provide deeper insights into gene regulation when combined with transcriptomics. The coordination and integration of all these complex networks to deduce gene regulation are major challenges for plant biologists. Python and R have emerged as major tools for managing complex scientific data over the past decade. In this study, we describe a reproducible protocol POTFUL (pant co-expression transcription factor regulators), implemented in Python 3, for integrating co-expression and transcription factor target protein networks to infer gene regulation.

Massive Splenomegaly with Pancytopenia in an Adult: Gaucher's Disease.

INTRODUCTION: Gaucher's disease (GD) is a rare lysosomal storage disease. It is characterized by the deposition of glucocerebroside in cells of the macrophage-monocyte system. GD presents a broad clinical expression, including hematologic abnormalities (such as pancytopenia), massive hepatosplenomegaly, diffuse infiltrative pulmonary disease, renal involvement in the form of nephropathy and glomerulonephritis, skeletal involvement in the form of bone pain, bony infarct, osteopenia, and pathological fracture. Based on the presence or absence of neurologic involvement, it is differentiated into type 1, type 2, and type 3. Gaucher's disease type 1 is the most common form, having the nonneuropathic form and carrying autosomal recessive traits. Gaucher's disease affects all racial and ethnic groups, while type 1 GD is most prevalent among Ashkenazi Jews. CASE PRESENTATION: A 20-year-old female was admitted to the medicine department with complaints of generalized weakness and easy fatigability, menorrhagia, and a dragging sensation in the abdomen. On clinical evaluation, she had bone marrow failure syndrome features along with massive splenomegaly. Later, she was confirmed with Gaucher disease type 1 disease by clinical and investigation (low ß-glucosidase level) evaluation. CONCLUSION: This case emphasizes keeping a differential diagnosis of glycogen storage disorder while evaluating a case of unexplained pancytopenia with massive splenomegaly in adulthood for an extended period. Currently, enzyme replacement therapy and substrate reduction therapy are the mainstay therapeutic options for GD.

Impact of secondary infections on dengue presentation: A cross-sectional study in a tertiary care hospital in Uttar Pradesh, India.

BACKGROUND: Recently, a wide range variety of manifestations, including a self­limiting to severe illness, has been increasingly reported in dengue. Few studies attract attention to severe dengue, mainly observed in secondary infection. With this background, this study aims to provide a comprehensive overview to differentiate primary from secondary dengue using serology (IgG) and the possible association of severity of illness in secondary dengue. METHODS: Present retrospective cross-sectional study was conducted at a North Indian tertiary care center from September 2021 to January 2022. Clinical data of confirmed dengue patients from the medicine department were collected and assigned as primary and secondary dengue. RESULTS: Of the 220 dengue patients, 22 (10 %) had secondary dengue infection. Hemorrhagic manifestations were reported in 58/220 (26.4 %) cases while 7/22 (31.8 %) in secondary dengue. Prevalent hemorrhagic manifestations in secondary dengue include purpura (27.3 %), vaginal bleeding (4.5 %), melaena (9.1 %), and epistaxis (4.5 %). In addition, 42 (19.1 %) patients had pancytopenia, and 8 (36.6 %) cases were of secondary dengue. Hepatic dysfunction was noted in 164 (74.5 %) cases. Notably, all secondary dengue cases (22;100 %) had hepatic dysfunction and severe in 9 (40.9 %) cases. In addition, in secondary dengue patients, evidence of plasma leakages such as hypoproteinemia 7 (31.8 %) and ascites (35 %) were statistically more frequent. Overall, two deaths (0.9 %) were reported, and were one in each group. CONCLUSIONS: Many parameters, including hemorrhagic manifestation (melaena), hematological characteristic (pancytopenia), evidence of plasma leakage (hypoproteinemia and ascites), gastrointestinal (GB wall thickening and hepatic dysfunction) and reduction in mean hemoglobin and platelet count were found to be statistically significant in secondary dengue infection. Additionally, early classification of secondary dengue may help to anticipate its severity and allow for early strategic intervention/management to lower morbidity and mortality.

Protein-Protein Interaction Network Analysis Using NetworkX.

In recent years, extracting information from biological data has become a particularly valuable way of gaining knowledge. Molecular interaction networks provide a framework for visualizing cellular processes, but their complexity frequently makes their interpretation difficult. Proteins are one of the primary determinants of biological function. Indeed, most biological activities in the living cells are functionally regulated by protein-protein interactions (PPIs). Thus, studying protein interactions is critical for understanding their roles within the cell. Exploring the PPI networks can open new avenues for future experimental studies and offer interspecies predictions for effective interaction mapping. In this chapter we will demonstrate how to construct, visualize, and analyze a protein-protein interaction network using NetworkX.