Lesion-remote astrocytes govern microglia-mediated white matter repair.

Spared regions of the damaged central nervous system undergo dynamic remodeling and exhibit a remarkable potential for therapeutic exploitation. Here, lesion-remote astrocytes (LRAs), which interact with viable neurons, glia and neural circuitry, undergo reactive transformations whose molecular and functional properties are poorly understood. Using multiple transcriptional profiling methods, we interrogated LRAs from spared regions of mouse spinal cord following traumatic spinal cord injury (SCI). We show that LRAs acquire a spectrum of molecularly distinct, neuroanatomically restricted reactivity states that evolve after SCI. We identify transcriptionally unique reactive LRAs in degenerating white matter that direct the specification and function of local microglia that clear lipid-rich myelin debris to promote tissue repair. Fueling this LRA functional adaptation is Ccn1 , which encodes for a secreted matricellular protein. Loss of astrocyte CCN1 leads to excessive, aberrant activation of local microglia with (i) abnormal molecular specification, (ii) dysfunctional myelin debris processing, and (iii) impaired lipid metabolism, culminating in blunted debris clearance and attenuated neurological recovery from SCI. Ccn1 -expressing white matter astrocytes are specifically induced by local myelin damage and generated in diverse demyelinating disorders in mouse and human, pointing to their fundamental, evolutionarily conserved role in white matter repair. Our findings show that LRAs assume regionally divergent reactivity states with functional adaptations that are induced by local context-specific triggers and influence disorder outcome. Astrocytes tile the central nervous system (CNS) where they serve vital roles that uphold healthy nervous system function, including regulation of synapse development, buffering of neurotransmitters and ions, and provision of metabolic substrates 1 . In response to diverse CNS insults, astrocytes exhibit disorder-context specific transformations that are collectively referred to as reactivity 2-5 . The characteristics of regionally and molecularly distinct reactivity states are incompletely understood. The mechanisms through which distinct reactivity states arise, how they evolve or resolve over time, and their consequences for local cell function and CNS disorder progression remain enigmatic. Immediately adjacent to CNS lesions, border-forming astrocytes (BFAs) undergo transcriptional reprogramming and proliferation to form a neuroprotective barrier that restricts inflammation and supports axon regeneration 6-9 . Beyond the lesion, spared but dynamic regions of the injured CNS exhibit varying degrees of synaptic circuit remodeling and progressive cellular responses to secondary damage that have profound consequences for neural repair and recovery 10,11 . Throughout these cytoarchitecturally intact, but injury-reactive regions, lesion-remote astrocytes (LRAs) intermingle with neurons and glia, undergo little to no proliferation, and exhibit varying degrees of cellular hypertrophy 7,12,13 . The molecular and functional properties of LRAs remain grossly undefined. Therapeutically harnessing spared regions of the injured CNS will require a clearer understanding of the accompanying cellular and molecular landscape. Here, we leveraged integrative transcriptional profiling methodologies to identify multiple spatiotemporally resolved, molecularly distinct states of LRA reactivity within the injured spinal cord. Computational modeling of LRA-mediated heterotypic cell interactions, astrocyte-specific conditional gene deletion, and multiple mouse models of acute and chronic CNS white matter degeneration were used to interrogate a newly identified white matter degeneration-reactive astrocyte subtype. We define how this reactivity state is induced and its role in governing the molecular and functional specification of local microglia that clear myelin debris from the degenerating white matter to promote repair.

Potential role of oxytocin in the regulation of memories and treatment of memory disorders.

Oxytocin (OXT) is an "affiliative" hormone or neurohormone or neuropeptide consists of nine amino acids, synthesized in magnocellular neurons of paraventricular (PVN) and supraoptic nuclei (SON) of hypothalamus. OXT receptors are widely distributed in various region of brain and OXT has been shown to regulate various social and nonsocial behavior. Hippocampus is the main region which regulates the learning and memory. Hippocampus particularly regulates the acquisition of new memories and retention of acquired memories. OXT has been shown to regulate the synaptic plasticity, neurogenesis, and consolidation of memories. Further, findings from both preclinical and clinical studies have suggested that the OXT treatment improves performance in memory related task. Various trials have suggested the positive impact of intranasal OXT in the dementia patients. However, these studies are limited in number. In the present study authors have highlighted the role of OXT in the formation and retrieval of memories. Further, the study demonstrated the outcome of OXT treatment in various memory and related disorders.

Gastrointestinal Stromal Tumor: A Clinicopathological Study and Management.

Background and aim Gastrointestinal stromal tumors (GISTs) account for a major portion of gastrointestinal mesenchymal tumors. The purpose of the current study is to examine the clinicopathological features, management, and therapeutic outcomes of primary GIST in a tertiary care hospital.  Materials and methods This is a prospective observational analysis. Seventeen patients with GIST have been detected and treated in the Department of Surgery of a tertiary care hospital with an attached medical institution over the last seven years. The clinical presentation, diagnosis method, tumor locations, histopathological results, surgical treatment, and postoperative results were analyzed.  Results There were six females and 11 males with ages ranging between 35 to 72 years. All the patients had symptoms, with abdominal pain the most prevalent. The most frequent primary site for GIST was the stomach (60-70%), followed by the small intestine (25-30%), the rectum, the esophagus, and the colon (2%). Preoperative diagnosis was made through endoscopy and a contrast-enhanced CT scan. Ninety-two percent of the cases tested positive for CD117. Surgery has been conducted for all 17 patients, with the liver being the most common site of metastasis. Imatinib and sunitinib increased the survival as well as postoperative recurrence rate while decreasing metastasis.  Conclusions The most general symptom of GIST was abdominal pain. In most instances, it was treated with surgery as well as adjuvant imatinib and sunitinib, and had a favorable prognosis. With increasing size and mitotic activity, the five-year survival rate falls, and the prognosis worsens.

Hemophagocytic Lymphohistiocytosis After Dengue Fever and Its Ocular Features.

This case report discusses a diagnosis of hemophagocytic lymphohistiocytosis in a man aged 40 years with a history of dengue fever.

Ocular manifestations following COVID-19 vaccination.

BACKGROUND: Immunologic and inflammatory adverse effects following vaccination against COVID-19 are being reported. While some reactions may develop denovo others concern its immunogenic effect in patients with pre-existing inflammatory conditions. METHODS: Retrospective consecutive patients diagnosed with ocular inflammatory manifestations within 8 weeks of receiving COVID-19 vaccination who presented to a tertiary eye care centre in South India. RESULTS: Ninety-eight eyes of 67 patients presenting with ocular inflammatory manifestations within 8 weeks following COVID-19 vaccination were studied. The mean age was 43 years (+/- 14.82; range 19-80 years). The most common presentations were anterior uveitis (n = 31, 31.7%), followed by panuveitis (n = 24, 24.5%). The mean time to onset of symptoms was 25 days (+/- 15.48; range 2-55 days) following a dose of vaccine. Among all patients, 39 (58.2%) had a previous history of ocular inflammation. Mean presenting visual acuity was 0.4 (0-4) logMAR units and mean final visual acuity was 0.2 (0-4) logMAR units. The causes for reduced vision included of cystoid macular edema (n=2, 2%), chorioretinal atrophy (n=2.2%), optic atrophy (n=1.1%), retinal vascular occlusion (n=1.1%) and acute retinal necrosis (n=1.1%). CONCLUSION: Infective and immunogenic adverse events should be watched out for after COVID-19 vaccination. It is difficult to establish causality for such manifestations, nevertheless, most of them were mild and had good final visual outcomes.

Systemic and Ophthalmic Manifestations of Chikungunya Fever.

PURPOSE: Chikungunya is a re-emerging viral infection across the globe. The purpose of this article is to review the systemic and ophthalmic manifestations associated with chikungunya fever. METHOD: A review of literature was conducted using online databases. RESULTS: In this report, we have reviewed the presently available literature on uveitis caused by chikungunya and highlighted the current knowledge of its clinical manifestations, imaging features, laboratory diagnostics, and the available therapeutic modalities from the systemic and ophthalmic standpoint. CONCLUSIONS: Ocular involvement in chikungunya infection may occur at the time of systemic manifestations or it may occur as a delayed presentation many weeks after the fever. Treatment relies on a supportive therapy for systemic illness. Treatment of ocular manifestation depends on the type of manifestations and usually includes a combination of topical and oral steroids.

Choroidal Involvement and Chronic Macular Edema in Acute Retinal Necrosis: A Novel Finding and a Novel Treatment.

Acute retinal necrosis (ARN) as the term suggests is recognized as necrotic inflammation of retina, in contrast to toxoplasma retinochoroiditis where involvement of choroid can be appreciated as choroidal thickening on optical coherence tomography scan during active stage. Secondly, sequelae of ARN, such as chronic anterior uveitis and cystoid macular edema, could be challenging to manage as steroid use in various forms poses a risk of virus reactivation. We present a case of ARN caused by varicella zoster virus with an initial confusing clinical picture with toxoplasma retinochoroiditis, documented with choroidal involvement. The patient also developed a chronic anterior uveitis with macular edema after resolution of ARN which was treated with topical interferon (IFN) alfa 2b therapy with successful outcome. This report supports the recently described choroidal involvement in ARN and suggests topical IFN as a novel treatment in management of chronic macular edema post ARN.

Pole-to-pole involvement of varicella zoster virus reactivation following COVID-19 vaccination.

The aim of this study is to report the clinical features, imaging findings including confocal imaging, corneal nerve fiber analysis, and management outcomes in a series of three cases of varicella zoster virus (VZV) reactivation following one dose of coronavirus disease 2019 (COVID-19) vaccination. This was a retrospective and observational study. All the patients who developed uveitis post-vaccination were pooled together. Patients who had VZV reactivation were included. Two cases had polymerase chain reaction positive for VZV from aqueous humor. At the time of presentation, IgG and IgM spike protein antibodies for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were tested. Out of this pool, three patients with classical features to describe pole-to-pole manifestations were chosen. A 36-year-old lady with post-vaccination sclerokeratouveitis associated with reactivation of herpes zoster ophthalmicus, a 56-year-old lady with post-vaccination acute anterior uveitis associated with herpes zoster ophthalmicus, and a 43-year-old gentleman with post-vaccination acute retinal necrosis were included. We present a possible link between anti-SARS-CoV-2 virus vaccination and varicella zoster reactivation in these patients and also describe the clinical features, imaging findings including confocal imaging, corneal nerve fiber analysis, and management with detailed discussion.

Estimating the Effect of Aerobic Exercise Training on Novel Lipid Biomarkers: A Systematic Review and Multivariate Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Aerobic exercise training (AET) prescribed as lipid management treatment positively affects the standard lipid profile and reduces cardiovascular disease (CVD) risk. Apolipoproteins, lipid and apolipoprotein ratios, and lipoprotein sub-fractions may more effectively predict CVD risk than the standard lipid profile but an AET response in these biomarkers has not been established. OBJECTIVES: We conducted a quantitative systematic review of randomised controlled trials (RCTs) to (1) determine the effects of AET on lipoprotein sub-fractions, apolipoproteins and relevant ratios; and (2) identify study or intervention covariates associated with change in these biomarkers. METHODS: We searched PubMed, EMBASE, all Web of Science and EBSCO health and medical online databases from inception to 31 December 2021. We included published RCTs of adult humans with ≥ 10 per group of participants; an AET intervention duration ≥ 12 weeks of at least moderate intensity (> 40% maximum oxygen consumption); and reporting pre/post measurements. Non-sedentary subjects, or those with chronic disease other than Metabolic Syndrome factors, or pregnant/lactating, as well as trials testing diet/medications, or resistance/isometric/unconventional training interventions, were excluded. RESULTS: Fifty-seven RCTs totalling 3194 participants were analysed. Multivariate meta-analysis showed AET significantly raised antiatherogenic apolipoproteins and lipoprotein sub-fractions (mmol/L mean difference (MD) 0.047 (95% confidence interval (CI) 0.011, 0.082), P = .01); lowered atherogenic apoliproteins and lipoprotein sub-fractions (mmol/L MD - 0.08 (95% CI - 0.161, 0.0003), P = .05); and improved atherogenic lipid ratios (MD - 0.201 (95% CI - 0.291, - 0.111), P < .0001). Multivariate meta-regression showed intervention variables contributed to change in lipid, sub-fraction, and apoliprotein ratios. CONCLUSION: Aerobic exercise training positively impacts atherogenic lipid and apolipoprotein ratios, alipoproteins, and lipoprotein sub-fractions; and antiatherogenic apolipoproteins and lipoprotein sub-fractions. Cardiovascular disease risk predicted by these biomarkers may be lowered when AET is prescribed as treatment or prevention. PROSPERO ID: CRD42020151925.

Need to Incorporate Endovascular Neurosurgery in Neurosurgery Curriculum in India: Stay Abreast or be Left Behind.

Endovascular neurosurgery is one of the most rapidly evolving subspecialties in the field of neurosurgery. Since its inception, it has taken up almost 50%-60% of the cerebrovascular workload. Various specialties are competing to claim this field; still, no one can argue against a neurosurgeon's suitability in performing endovascular techniques. Currently, the field is shared between neurosurgeons and neuroradiologists, each getting different pie shares in various parts of the world. However, in India, barring a few residency programs, most neurosurgery programs offer little or no exposure to endovascular techniques. There is an urgent need for endovascular neurosurgery to be incorporated in the neurosurgery training curriculum in the country. Performing DSAs is the first step toward starting an endovascular neurosurgery unit. We have presented here the data of the DSAs done by a single neurosurgeon over almost 3 years. We have discussed our experience in the hope that fellow neurosurgeons across the country find it useful.

Improving and Promoting Social Determinants of Health at a System Level.

BACKGROUND: Social determinants of health (SDoH), such as low socioeconomic status, race and ethnicity, poor environmental conditions, food insecurity, and inadequate access to health care services, are known to adversely affect health outcomes. The aim of this project is to address SDoH needs with clinical care to further improve patient outcomes and assist safe discharge. APPROACH: Prime Healthcare Service's model to address SDoH needs focused on supplementing its existing care coordination process with digital innovation while leveraging its highly skilled multidisciplinary team of physicians and mid-level providers, care coordinators, case managers, and social workers and strengthening its relationships with community partners. Prime extended the scope of its services by growing its providers and care navigators' presence in the community to assess needs and foster hospital-community relationships to meet the needs of individual patients. RESULTS: The 2021 Lown Hospital Index, which includes matrices Equity, Value, and Outcomes, has ranked Prime Healthcare Services, as a system, #1 overall in New Jersey and Nevada states. It also ranked Saint Michael's Medical Center number 2 in New Jersey for social responsibility, Centinela Hospital Medical Center number 9 in California for clinical outcomes, and St. Joseph Medical Center number 3 in Missouri for outcomes. The Index also ranked North Vista Hospital as the number 1 most racially inclusive hospital in Nevada. The acute myocardial infarction (AMI) 30-day risk-standardized mortality rate was reduced by an average 1% across the system, while the risk-standardized AMI complication rate was at 0%. CONCLUSION: Development of an SDoH screening tool, prioritizing high-risk factors, involving a multidisciplinary team, and strengthening the post-acute network have helped address and link the role of SDoH factors in patient outcomes and has resulted in reduced readmission rate, lower mortality and complications rate, and improved cost alignment with the Centers for Medicare & Medicaid Services payment reforms initiative and value-based care.

Advance Teaching of Fundamentals of Homoeopathy (ATFH): redefining competency based approach

The curriculumin academic medicine is defined by writing effective Learning objectives (LO). LO iselaborated based on perceptions of unbiased written aspects,of course, the rationale in statements is explained and tested through the completion of educational activity. These are the foundations for defining the outcomes in building up strong educational policieswhich are instructionalaligned through predefined effective curriculum courseswith added mapped outcomes. This letter provides the ongoing aspect of the development of Homoeopathic education in India regulated by the National Commission for Homoeopathy for the subject course of Advance Teaching of Fundamentals of Homoeopathy (ATFH). The essential components for the ATFHsubject course with LO and outcome assessment is been discussed and would provide a new arena of academic research in building up rationale in the programed [Doctor of Homoeopathy(MD,(Hom).

Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip.

Mechanical breathing motions have a fundamental function in lung development and disease, but little is known about how they contribute to host innate immunity. Here we use a human lung alveolus chip that experiences cyclic breathing-like deformations to investigate whether physical forces influence innate immune responses to viral infection. Influenza H3N2 infection of mechanically active chips induces a cascade of host responses including increased lung permeability, apoptosis, cell regeneration, cytokines production, and recruitment of circulating immune cells. Comparison with static chips reveals that breathing motions suppress viral replication by activating protective innate immune responses in epithelial and endothelial cells, which are mediated in part through activation of the mechanosensitive ion channel TRPV4 and signaling via receptor for advanced glycation end products (RAGE). RAGE inhibitors suppress cytokines induction, while TRPV4 inhibition attenuates both inflammation and viral burden, in infected chips with breathing motions. Therefore, TRPV4 and RAGE may serve as new targets for therapeutic intervention in patients infected with influenza and other potential pandemic viruses that cause life-threatening lung inflammation.

Ectopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ-on-a-Chip.

Lymphoid follicles (LFs) are responsible for generation of adaptive immune responses in secondary lymphoid organs and form ectopically during chronic inflammation. A human model of ectopic LF formation will provide a tool to understand LF development and an alternative to non-human primates for preclinical evaluation of vaccines. Here, it is shown that primary human blood B- and T-lymphocytes autonomously assemble into ectopic LFs when cultured in a 3D extracellular matrix gel within one channel of a two-channel organ-on-a-chip microfluidic device. Superfusion via a parallel channel separated by a microporous membrane is required for LF formation and prevents lymphocyte autoactivation. These germinal center-like LFs contain B cells expressing Activation-Induced Cytidine Deaminase and exhibit plasma cell differentiation upon activation. To explore their utility for seasonal vaccine testing, autologous monocyte-derived dendritic cells are integrated into LF Chips. The human LF chips demonstrate improved antibody responses to split virion influenza vaccination compared to 2D cultures, which are enhanced by a squalene-in-water emulsion adjuvant, and this is accompanied by increases in LF size and number. When inoculated with commercial influenza vaccine, plasma cell formation and production of anti-hemagglutinin IgG are observed, as well as secretion of cytokines similar to vaccinated humans over clinically relevant timescales.

Bilateral Post Fever Retinitis With Retinal Vascular Occlusions Following Severe Acute Respiratory Syndrome Corona Virus (SARS-CoV2) Infection.

INTRODUCTION: As the world fights the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several reports of retinal manifestations of the disease are emerging. Post fever retinitis is a well reported ocular inflammatory reaction to multiple invasive agents, be it virus, bacteria or other microbial agent. PURPOSE: We report an interesting case of bilateral multifocal retinitis with multiple vascular occlusions in a patient, three weeks after a febrile illness. RESULTS: Investigations to ascertain the cause of fever resulted in identifying ephemeral seropositivity for several different Ribonucleic acid (RNA) viruses. The retinitis was managed with systemic steroids, doxycycline and anticoagulants with improvement in vision. CONCLUSION: High and persistent seropositive response against (SARS-CoV-2) helped us to narrow it as the causative agent but the cross reactivity of SARS-CoV-2 with other viruses can be misleading and needs careful interpretation.

Reducing split-thickness skin grafting donor site agony; faster healing and decreased pain-role of platelet-rich plasma.

INTRODUCTION: The split-thickness skin graft harvested donor site is associated with prolonged healing, discomfort, and pain. Platelet-rich plasma (PRP) contains platelet-derived growth factors and has been widely used in chronic wounds and skin graft donor sites. PRP application is known to accelerate wound epithelialization rates, and also reduce postoperative wound site pain. MATERIALS AND METHODS: We assessed 20 patients admitted to our hospital service who underwent split-thickness skin grafting (STSGs) with proximal half of the donor site treated with PRP. The dressing was conducted on postoperative day 7, 14, and 21. The donor site healing was assessed with serial photographs and donor site pain measured by numerical rating scale. RESULTS: Complete healing of wounds (epithelialization) was present in 12 (60%) patients dressed with PRP. Pain on opening dressing was an average of 3.5 in PRP dressed wounds and 6.35 in control wounds. Patients dressed without PRP, none of them had complete epithelialization. All patients had partial healing and were less than the donor site dressed with PRP. Based on these results, skin graft donor site with PRP showed accelerated healing and reduced pain and discomfort compared to control without PRP. CONCLUSION: PRP is a beneficial adjunct for reducing donor site pain and increased healing of donor site following STSG harvest.

Revisiting prophylaxis of homeopathic interventions in COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused by novel beta-coronavirus has emerged as a cause of coronavirus pandemic (COVID-19) declared by Public Health Emergency of International Concern (PHEIC). Korean oriental medicine, Traditional Chinese Medicine (TCM), and Indian systems of medicine known as AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha and Sowa-Rigpa and Homeopathy) had implemented various prophylactic measures and interim treatment guidelines in prevention and treatment for COVID -19 cases. However, even though different approaches were implemented to break the epidemic chain, we have not reached herd effect or herd immunity in the Indian population. Therefore, in this ongoing COVID-19 pandemic, a specific study on immune markers of IL-6 (Interleukin-6), D-Dimer, Ferritine, CRP (C-reactive protein) with SARS CoV-2 specific IgG & IgM antibodies need to be investigated for generating hard-core evidence for homeoprophylaxis in terms of immunity response. Therefore, there seems to be a need to revisit the program of homeoprophylaxis in the COVID -19 pandemic.

Determining the effect size of aerobic exercise training on the standard lipid profile in sedentary adults with three or more metabolic syndrome factors: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To estimate the change in the standard lipid profile (SLP) of adults diagnosed with ≥3 metabolic syndrome (MetS) factors following aerobic exercise training (AET); and to investigate whether study/intervention covariates are associated with this change. DESIGN: Systematic review with univariate meta-analysis and meta-regression. DATA SOURCES: English language searches of online databases from inception until July 2020. ELIGIBILITY CRITERIA: (1) Published randomised controlled human trials with study population ≥10 per group; (2) sedentary adults with ≥3 MetS factors but otherwise free of chronic disease, not pregnant/lactating; (3) AET-only intervention with duration ≥12 weeks; and (4) reporting pre-post intervention SLP outcomes. RESULTS: Various univariate meta-analyses pooled 48 data sets of 2990 participants. Aerobic exercise training significantly (P<.001) improved all lipids (mmol/L mean difference ranges, 95% CIs): total cholesterol, -0.19 (-0.26 to -0.12) to -0.29 (-0.36 to -0.21); triglycerides, -0.17 (-0.19 to -0.14) to -0.18 (-0.24 to -0.13); high-density lipoprotein-cholesterol (HDL-C), 0.05 (0.03 to 0.07) to 0.10 (0.05 to 0.15); and low-density lipoprotein-cholesterol (LDL-C), -0.12 (-0.16 to -0.9) to -0.20 (-0.25 to -0.14). Meta-regression showed that intensity may explain change in triglycerides and volume may explain change in HDL-C and LDL-C. CONCLUSION: Aerobic exercise training positively changes the SLP of sedentary and otherwise healthy adults with ≥3 MetS factors. Adjusting AET intervention training variables may increase the effects of AET on triglycerides and HDL-C. PROSPERO REGISTRATION NUMBER: CRD42020151925.