Anatomical correlates for the newly discovered meningeal layer in the existing literature: A systematic review.

The existence of a previously unrecognized subarachnoid lymphatic-like membrane (SLYM) was reported in a recent study. SLYM is described as an intermediate leptomeningeal layer between the arachnoid and pia mater in mouse and human brains, which divides the subarachnoid space (SAS) into two functional compartments. Being a macroscopic structure, having missed detection in previous studies is surprising. We systematically reviewed the published reports in animals and humans to explore whether prior descriptions of this meningeal layer were reported in some way. A comprehensive search was conducted in PubMed/Medline, EMBASE, Google Scholar, Science Direct, and Web of Science databases using combinations of MeSH terms and keywords with Boolean operators from inception until 31 December 2023. We found at least eight studies that provided structural evidence of an intermediate leptomeningeal layer in the brain or spinal cord. However, unequivocal descriptions for this layer all along the central nervous system were scarce. Obscure names like the epipial, intermediate meningeal, outer pial layers, or intermediate lamella were used to describe it. Its microscopic/ultrastructural details closely resemble the recently reported SLYM. We further examined the counterarguments in current literature that are skeptical of the existence of this layer. The potential physiological and clinical implications of this new meningeal layer are significant, underscoring the urgent need for further exploration of its structural and functional details.

Naturally Derived Luminescent Material in Engineered Silk and Its Application as a Fluorescent Dye with a Large Stokes Shift and Sensing Capability.

Silkworms have provided valuable byproducts (spanning from high-quality textiles to health supplements) to humans for millennia. Despite their importance in sericultural economy and biotechnology, manifold possibilities inherent in the myriad natural or artificially generated silk varieties have been underestimated. In this paper, we report that the Yeonnokjam silk strain, which shows light-green color, contains quercetin fluorochrome (QueF) in sericin, and QueF can be used as a fluorescence dye with a large Stokes shift and high sensitivity to environmental temperature and pH, thus functioning as an environmental sensing material. A Stokes shift exceeding 180 nm, a quantum efficiency of 1.28%, and a rapid fluorescence decay of 0.67 ns are obtained, which are influenced by solvent polarities. Moreover, QueF can be used as a UV blocker as well, and its low cytotoxicity and biocompatibility further suggest promising prospects for diverse application in cosmetics and medical materials in the future.

Serum levels of hydroxylated metabolites of arachidonic acid cross-sectionally and longitudinally predict knee pain progression: an observational cohort study.

OBJECTIVE: To examine associations between serum oxylipins, which regulate tissue repair and pain signalling, and knee pain/radiographic osteoarthritis (OA) at baseline and knee pain at 3 year follow-up. METHOD: Baseline, and 3 year follow-up, knee pain phenotypes were assessed from 154 participants in the Knee Pain in the Community (KPIC) cohort study. Serum and radiographic Kellgren and Lawrence (KL) and Nottingham line drawing atlas OA scores were collected at baseline. Oxylipin levels were quantified using liquid chromatography coupled with mass spectrometry. Associations were measured by linear regression and receiver operating characteristics (ROC). RESULTS: Serum levels of 8,9-epoxyeicosatrienoic acid (EET) (ß(95% confidence intervals (CI)) = 1.809 (-0.71 to 2.91)), 14,15-dihydroxyeicosatrienoic acid (DHET) (ß(95%CI) = 0.827 (0.34-1.31)), and 12-hydroxyeicosatetraenoic acid (HETE) (ß(95%CI) = 4.090 (1.92-6.26)) and anandamide (ß(95%CI) = 3.060 (1.35-4.77)) were cross-sectionally associated with current self-reported knee pain scores (numerical rating scale (NRS) item 3, average pain). Serum levels of 9- (ß(95%CI) = 0.467 (0.18-0.75)) and 15-HETE (ß(95%CI) = 0.759 (0.29-1.22)), 14-hydroxydocosahexaenoic acid (ß(95%CI) = 0.483(0.24-0.73)), and the ratio of 8,9-EET:DHET (ß(95%CI) = 0.510(0.19-0.82)) were cross-sectionally associated with KL scores. Baseline serum concentrations of 8,9-EET (ß(95%CI) = 2.166 (0.89-3.44)), 5,6-DHET (ß(95%CI) = 152.179 (69.39-234.97)), and 5-HETE (ß(95%CI) = 1.724 (0.677-2.77) showed positive longitudinal associations with follow-up knee pain scores (NRS item 3, average pain). Combined serum 8,9-EET and 5-HETE concentration showed the strongest longitudinal association (ß(95%CI) = 1.156 (0.54-1.77) with pain scores at 3 years, and ROC curves distinguished between participants with no pain and high pain scores at follow-up (area under curve (95%CI) = 0.71 (0.61-0.82)). CONCLUSIONS: Serum levels of a combination of hydroxylated metabolites of arachidonic acid may have prognostic utility for knee pain, providing a potential novel approach to identify people who are more likely to have debilitating pain in the future.

Identification of potential serum biomarkers associated with HbA1c levels in Indian type 2 diabetic subjects using NMR-based metabolomics.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM), a progressive metabolic disorder characterized by chronic hyperglycemia and the development of insulin resistance, has increased globally, with worrying statistics coming from children, adolescents, and young adults from developing countries like India. Here, we investigated unique circulating metabolic signatures associated with prediabetes and T2DM in an Indian cohort using NMR-based metabolomics. MATERIALS AND METHODS: The study subjects included healthy volunteers (N = 101), prediabetic subjects (N = 75), and T2DM patients (N = 108). Serum metabolic profiling was performed using 1H NMR spectroscopy and major perturbed metabolites were identified by multivariate analysis and receiver operating characteristic (ROC) modules. RESULTS: Of the 36 aqueous abundant metabolites, 24 showed a statistically significant difference between healthy volunteers, prediabetics, and established T2DM subjects. On performing multivariate ROC curve analysis with 5 commonly dysregulated metabolites (namely, glucose, pyroglutamate, o-phosphocholine, serine, and methionine) in prediabetes and T2DM, AUC values obtained were 0.96 (95 % confidence interval (CI) = 0.93, 0.98) for T2DM; and 0.88 (95 % CI = 0.81, 0.93) for prediabetic subjects, respectively. CONCLUSION: We propose that the identified metabolite panel can be used in the future as a biomarker for clinical diagnosis, patient surveillance, and for predicting individuals at risk for developing diabetes.

Clinical profile of 1208 newly diagnosed colorectal cancer patients in Tamil Nadu-A multi-centric survey.

BACKGROUND: An increasing incidence of colorectal cancer (CRC) is being reported in developing countries, including India. Most Indian studies on CRC are retrospective and single-centered. The present study is an attempt to understand the current clinical profile and stage of newly diagnosed CRCs across multiple centers in Tamil Nadu, India. METHODS: A multi-centric observational survey was conducted between September 1, 2021, and August 31, 2022, under the aegis of the Indian Society of Gastroenterology - Tamil Nadu chapter. Patients 18 years of age and older with a recent diagnosis of CRC fulfilling the inclusion criteria were prospectively recruited at the participating centers. Their demographic, clinical, biochemical, endoscopic, histopathologic, radiologic and risk factor details were systematically collected and analyzed. RESULTS: Across 23 centers in Tamil Nadu, 1208 patients were recruited. The male:female ratio was 1.49:1, while mean (SD) age was 57.7 (13.5) years. A majority (81.9%) were Tamils and 78.5% belonged to lower socioeconomic classes. The predominant symptoms were hematochezia (30.2%) and a change in bowel habits (27.5%). The most common locations were the rectum (34.3%) and rectosigmoid (15.1%). Synchronous CRCs were seen in 3.3% and synchronous colorectal polyps in 12.8%. Predisposing factors for CRC were seen in 2%. A past history of any cancer among CRC patients was obtained in 3.1% and a family history of any cancer was found in 7.6%. Patients who were either overweight or obese constituted 46.4% of the study population. At presentation, the predominant stages were stage III (44.7%) and stage IV (20.8%). CONCLUSIONS: A majority of patients with newly diagnosed CRC in Tamil Nadu belonged to the lower socioeconomic classes. About 60% had CRCs located within the reach of the flexible sigmoidoscope. Two-thirds of the patients exceeded stage II disease at presentation. TRIAL REGISTRATION: Not applicable.

The Effect of Acute Knee Injuries and Related Knee Surgery on Serum Levels of Pro- and Anti-inflammatory Lipid Mediators and Their Associations With Knee Symptoms.

BACKGROUND: Despite an acute knee injury being a major risk factor for osteoarthritis, the factors that initiate and maintain this risk of longer-term knee symptoms are poorly understood. Bioactive lipids derived from omega-3 and -6 polyunsaturated fatty acids have key roles in the regulation of the inflammatory response and have been linked to joint damage and osteoarthritis pain in translational models. HYPOTHESIS: There would be associations between systemic levels of bioactive lipids and knee symptoms longitudinally after an acute knee injury and related knee surgery. STUDY DESIGN: Controlled laboratory study. METHODS: This study analyzed a subset of young, active adults who had sustained an acute knee injury (recruited via a surgical care pathway) and healthy age- and sex-matched controls. Surgery, if performed, was conducted after the baseline serum sample was taken and before the 3-month and 2-year visits. Liquid chromatography-tandem mass spectrometry of 41 bioactive lipids was carried out in sera of (1) 47 injured participants (median age, 28 years) collected at baseline (median, 24 days after injury), 3 months, and 2 years, along with the Knee injury and Osteoarthritis Outcome Score, and (2) age- and sex-matched controls. RESULTS: Levels of the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (P≤ .0001) and docosahexaenoic acid (P≤ .0001) and the pro-resolving lipid mediators 17- and 14-hydroxydocosahexaenoic acid, and 18-hydroxyeicosapentaenoic acid were all significantly greater at baseline in injured participants compared with the later time points and also higher than in healthy controls (P = .0019 and P≤ .0001, respectively). Levels of pro-inflammatory prostaglandins E2 and D2, leukotriene B4, and thromboxane B2 were significantly lower at baseline compared with the later time points. Higher levels of 8,9-, 11,12-, and 14,15-dihydroxyeicosatrienoic acid (DHET) were cross-sectionally associated with more severe knee pain/symptoms according to the Knee injury and Osteoarthritis Outcome Score at 2 years (P = .0004, R2 = 0.251; P = .0002, R2 = 0.278; and P = .0012, R2 = 0.214, respectively). CONCLUSION: The profile of pro-resolving versus pro-inflammatory lipids at baseline suggests an initial activation of pro-resolution pathways, followed by the later activation of pro-inflammatory pathways. CLINICAL RELEVANCE: In this largely surgically managed cohort, the association of soluble epoxide hydrolase metabolites, the DHETs, with more severe knee symptoms at 2 years provides a rationale for further investigation into the role of this pathway in persisting knee symptoms in this population, including potential therapeutic strategies.

ARL8B mediates lipid droplet contact and delivery to lysosomes for lipid remobilization.

Lipid droplets (LDs) play a crucial role in maintaining cellular lipid balance by storing and delivering lipids as needed. However, the intricate lipolytic pathways involved in LD turnover remain poorly described, hindering our comprehension of lipid catabolism and related disorders. Here, we show a function of the small GTPase ARL8B in mediating LD turnover in lysosomes. ARL8B-GDP localizes to LDs, while ARL8-GTP predominantly favors lysosomes. GDP binding induces a conformation with an exposed N-terminal amphipathic helix, enabling ARL8B to bind to LDs. By associating with LDs and lysosomes, and with its property to form a heterotypic complex, ARL8B mediates LD-lysosome contacts and efficient lipid transfer between these organelles. In human macrophages, this ARL8B-dependent LD turnover mechanism appears as the major lipolytic pathway. Our finding opens exciting possibilities for understanding the molecular mechanisms underlying LD degradation and its potential implications for inflammatory disorders.

Sharing of proximal fibers by the anterolateral and lateral collateral ligaments in the human knee: a cadaveric study.

Literature is highly inconsistent in describing the proximal attachment of the anterolateral ligament (ALL) and its relationship with the lateral collateral ligament (LCL) in human knees. This observational study aims to investigate that lacuna. The gross dissection was performed in the lower limbs (n = 83) from the donated adult-age (> 18 years) embalmed cadavers from medical institutions in the north and east India. The dissected knee specimens were first examined macroscopically. Further routine and special staining and microscopic examinations were performed. The ALL was absent in approximately 20.4% of the studied knee specimens (17/83). In remaining, the sharing of ALL and LCL proximal fibers was observed as a consistent finding (~ 97%) with rare exceptions. The mean length of the tibial and meniscal limbs of ALL was 1.57 ± 0.8 cm [Range (R) 0.5-4 cm] and 0.73 ± 0.47 cm [Range (R) 0.1-1.6 cm], respectively. In addition, multiple variations in its presentation were observed. We propose that the proximal sharing of LCL-ALL fibers is a dominant feature in the studied population. The sharing of the fibers may impact the biomechanics and injury mechanisms for both ligaments. The possibility of ethnic variations in the ALL morphology should be a concern during reconstruction surgery.

Salvage of a severely mangled limb following traumatic injury.

Management of a severely damaged extremity poses a dilemma-whether to perform a primary amputation or attempt limb salvage. A multitude of factors-such as the extent of neurovascular injury, limb ischaemia time, severity of bone and soft tissue loss, physiological reserve of the patient and availability of surgical expertise and resources-influence this decision. The Mangled Extremity Severity Score (MESS) was developed as a predictor of the need for limb amputation, and a MESS of 7 or more is considered a predictor of primary amputation. Here we describe a case where a man in his 20s sustained traumatic avulsion of his right ankle with severe neurovascular damage and multiple tendon injuries onboard a ship at high sea. Despite a MESS of 10, limb ischaemia time of more than 10 hours and injuries to all three extremity vessels (anterior tibial, posterior tibial and peroneal arteries), limb salvage was successfully carried out at a level-II trauma centre.

SARS-CoV-2 Omicron Variant Genomic Sequences and Their Epidemiological Correlates Regarding the End of the Pandemic: In Silico Analysis.

Background: Emergence of the new SARS-CoV-2 variant B.1.1.529 worried health policy makers worldwide due to a large number of mutations in its genomic sequence, especially in the spike protein region. The World Health Organization (WHO) designated this variant as a global variant of concern (VOC), which was named "Omicron." Following Omicron's emergence, a surge of new COVID-19 cases was reported globally, primarily in South Africa. Objective: The aim of this study was to understand whether Omicron had an epidemiological advantage over existing variants. Methods: We performed an in silico analysis of the complete genomic sequences of Omicron available on the Global Initiative on Sharing Avian Influenza Data (GISAID) database to analyze the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. In addition, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period from October 1 to November 29, 2021) with matched epidemiological data (new COVID-19 cases and deaths) from South Africa. Results: Compared with the current list of global VOCs/variants of interest (VOIs), as per the WHO, Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with the Alpha variant for the complete sequence and the RBM. The mutations were found to be primarily condensed in the spike region (n=28-48) of the virus. Further mutational analysis showed enrichment for the mutations decreasing binding affinity to angiotensin-converting enzyme 2 receptor and receptor-binding domain protein expression, and for increasing the propensity of immune escape. An inverse correlation of Omicron with the Delta variant was noted (r=-0.99, P<.001; 95% CI -0.99 to -0.97) in the sequences reported from South Africa postemergence of the new variant, subsequently showing a decrease. There was a steep rise in new COVID-19 cases in parallel with the increase in the proportion of Omicron isolates since the report of the first case (74%-100%). By contrast, the incidence of new deaths did not increase (r=-0.04, P>.05; 95% CI -0.52 to 0.58). Conclusions: In silico analysis of viral genomic sequences suggests that the Omicron variant has more remarkable immune-escape ability than existing VOCs/VOIs, including Delta, but reduced virulence/lethality than other reported variants. The higher power for immune escape for Omicron was a likely reason for the resurgence in COVID-19 cases and its rapid rise as the globally dominant strain. Being more infectious but less lethal than the existing variants, Omicron could have plausibly led to widespread unnoticed new, repeated, and vaccine breakthrough infections, raising the population-level immunity barrier against the emergence of new lethal variants. The Omicron variant could have thus paved the way for the end of the pandemic.

Association of BCC Module Roll-Out in SHG meetings with changes in complementary feeding and dietary diversity among children (6-23 months)? Evidence from JEEViKA in Rural Bihar, India.

OBJECTIVES: Child dietary diversity is very low across rural communities in Bihar. Based on the experience of behavior change communication (BCC) module roll out in self-help group (SHG) sessions in rural Bihar, this study aims to assess the impact of the intervention on child dietary diversity levels in the beneficiary groups. METHODS: The study is based on a pre-post study design whereby child dietary diversity is examined for a sample of 300 children (6-23 months old from 60 village organizations) during both pre-intervention as well as post-intervention phase. The latter consists of two types of group viz. a) children whose mothers were directly exposed to BCC module in SHGs sessions and b) those who were non-participants but may have indirect exposure through spillovers of BCC activities. Econometric analysis including logistic regression as well as propensity score matching techniques are applied for estimating the changes in dietary diversity in the post-intervention phase. RESULTS: During the pre-intervention phase, 19% of the children (6-23 months) had adequate dietary diversity (eating from at least 4 out of 7 different food groups) and this increased to 49% among the exposed group and to 28% among the non-exposed group in the post-intervention phase. The exposed group have an odds ratio of 3.81 (95% CI: 2.03, 7.15) for consuming diverse diet when compared to the pre-intervention group. The propensity score matching analysis finds a 33% average treatment effect on the treated (ATT) for the group participating in BCC sessions at SHG events. CONCLUSION: BCC roll out among SHG members is an effective mode to increase dietary diversity among infants and young children. The impact on child dietary diversity was significantly higher among mothers directly exposed to BCC modules. The BCC module also improved knowledge and awareness levels on complementary feeding and child dietary diversity.

Cellulose paper sorptive extraction (CPSE): A simple and affordable microextraction method for analysis of basic drugs in blood as a proof of concept.

Aiming towards simplifying sample preparation procedure, the present work explores use of unmodified laboratory filter paper as sorbent for extraction of nine basic drugs (five antidepressants, four benzodiazepines, and ketamine) from human blood samples and their analysis by gas chromatography-mass spectrometry (GC-MS). The procedure termed as cellulose paper sorptive extraction (CPSE) is straightforward. It involves adsorption of target analytes from deproteinized diluted blood samples on the unmodified cellulose paper followed by elution into 2 mL of methanol. Multivariate optimization, consisting of Placket-Burman design (PBD) and central composite design (CCD), was used to screen and optimize significant factors for CPSE. The proposed method follows the principles of green analytical chemistry (GAC), as the unmodified filter paper used as the sorbent is inexpensive and biodegradable. The technique is easy to perform and requires only 2 mL of MeOH during the entire extraction procedure. Under the optimized conditions, the limit of detection and quantification for the target analytes were estimated to be in the range of 0.003-0.035 and 0.010-0.117 µg mL-1, respectively. In contrast, the relative standard deviations were consistently below 10 %. The calibration curves were linear in the range of 0.015-2 µg mL-1 with a coefficient of determination (R2) in the range of 0.995-0.999.Satisfactory recoveries ranging from 87 to 99 % was achieved. As proof of concept, the analysis of nine drugs in blood samples from the patients was performed to demonstrate the potential application of the proposed method.

COVID-19 vaccination may enhance hippocampal neurogenesis in adults.

Emerging evidence suggests a detrimental impact of COVID-19 illness on the continued hippocampal neurogenesis in adults. In contrast, the existing literature supports an enhancing effect of COVID-19 vaccination on adult hippocampal neurogenesis. Vaccines against respiratory infections, including influenza, have been shown to enhance hippocampal neurogenesis in adult-age animals. We propose that a similar benefit may happen in COVID-19 vaccinated adults. The vaccine-induced enhancement of the hippocampal neurogenesis in adults thus may protect against age-related cognitive decline and mental disorders. It alsohints at an added mental health benefit of the COVID-19 vaccination programs in adults.

"Partial Open Sky Method" - A novel technique to avoid the open sky condition during Triple procedure or Penetrating keratoplasty.

Penetrating keratoplasty is referred to as an "open-sky" procedure because the intraocular contents are entirely exposed to atmospheric pressure after the diseased cornea has been trephined off and before the donor button is sutured. Suprachoroidal hemorrhage (SCH) is a major vision-threatening complication, associated with this open-sky procedure. While numerous factors may predispose an eye to SCH, like hypertension, myopia, trauma, glaucoma, etc., it is better to be prepared for the worst eventuality. We described a novel technical modification, denoted as the "partial open sky technique", that we used during the surgical steps of trephining and excision of host corneal tissue in seven cases of triple procedure and penetrating keratoplasty in our center over two months. We propose that the technique would be additionally helpful in managing the inadvertent suprachoroidal hemorrhage associated with keratoplasty over the available existing methods. Abbreviations: SCH = Suprachoroidal hemorrhage, ICCE = Intracapsular cataract surgery, ECCE = Extracapsular cataract surgery, WTW = White to White.

Engineering Silk Protein to Modulate Polymorphic Transitions for Green Lithography Resists.

Silk protein is being increasingly introduced as a prospective material for biomedical devices. However, a limited locus to intervene in nature-oriented silk protein makes it challenging to implement on-demand functions to silk. Here, we report how polymorphic transitions are related with molecular structures of artificially synthesized silk protein and design principles to construct a green-lithographic and high-performative protein resist. The repetition number and ratio of two major building blocks in synthesized silk protein are essential to determine the size and content of ß-sheet crystallites, and radicals resulting from tyrosine cleavages by the 193 nm laser irradiation induce the ß-sheet to α-helix transition. Synthesized silk is designed to exclusively comprise homogeneous building blocks and exhibit high crystallization and tyrosine-richness, thus constituting an excellent basis for developing a high-performance deep-UV photoresist. Additionally, our findings can be conjugated to design an electron-beam resist governed by the different irradiation-protein interaction mechanisms. All synthesis and lithography processes are fully water-based, promising green lithography. Using the engineered silk, a nanopatterned planar color filter showing the reduced angle dependence can be obtained. Our study provides insights into the industrial scale production of silk protein with on-demand functions.

A Bioinformatics Tool for Predicting Future COVID-19 Waves Based on a Retrospective Analysis of the Second Wave in India: Model Development Study.

Background: Since the start of the COVID-19 pandemic, health policymakers globally have been attempting to predict an impending wave of COVID-19. India experienced a devastating second wave of COVID-19 in the late first week of May 2021. We retrospectively analyzed the viral genomic sequences and epidemiological data reflecting the emergence and spread of the second wave of COVID-19 in India to construct a prediction model. Objective: We aimed to develop a bioinformatics tool that can predict an impending COVID-19 wave. Methods: We analyzed the time series distribution of genomic sequence data for SARS-CoV-2 and correlated it with epidemiological data for new cases and deaths for the corresponding period of the second wave. In addition, we analyzed the phylodynamics of circulating SARS-CoV-2 variants in the Indian population during the study period. Results: Our prediction analysis showed that the first signs of the arrival of the second wave could be seen by the end of January 2021, about 2 months before its peak in May 2021. By the end of March 2021, it was distinct. B.1.617 lineage variants powered the wave, most notably B.1.617.2 (Delta variant). Conclusions: Based on the observations of this study, we propose that genomic surveillance of SARS-CoV-2 variants, complemented with epidemiological data, can be a promising tool to predict impending COVID-19 waves.

Can lubrication of the eyelid speculum reduce overall pain perception associated with cataract surgery by phacoemulsification performed under topical anesthesia?

Purpose: This study aimed to evaluate the effect of using the lubricated eyelid speculum on the overall pain perception by the subject patients who underwent cataract surgery by phacoemulsification technique under topical anesthesia. Methods: A prospective interventional randomized comparative study was conducted at the tertiary eye care center, wherein adult patients scheduled for bilateral cataract surgery with phacoemulsification techniques under topical anesthesia were randomized to undergo surgery with two different modes of eyelid speculum insertion, either with or without lubrication of the eyelid speculum. Fifty percent of the patients underwent surgery with eyelid speculum without lubrication, and 50% with lubrication of the eyelid speculum. The primary outcome was to compare the level of overall pain perception among the subject patients of the two groups by using the Visual Analogue Scale (VAS) in the immediate postoperative period. Results: The study included 130 patients who underwent bilateral cataract surgery (n = 260 eyes) under topical anesthesia, wherein n = 130 eyes underwent surgery using lubricated eyelid speculum and n = 130 eyes underwent surgery with dry eyelid speculum. Pain perception score assessed on the VAS (0-10 cm) ranged from 0.5 to 6, with a mean ± standard deviation of 2.06 ± 1.12. A significant correlation was found with two different methods of eyelid speculum insertion with reduced overall pain perception in patients with the use of lubricated eyelid speculum compared to the dry eyelid speculum (P = 0.0001). Conclusion: The overall pain perception associated with cataract surgery performed by phacoemulsification technique under topical anesthesia can be further minimized by lubricating the eyelid speculum prior to insertion for exposing the globe.

Serum Levels of Proinflammatory Lipid Mediators and Specialized Proresolving Molecules Are Increased in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 and Correlate With Markers of the Adaptive Immune Response.

BACKGROUND: Specialized proresolution molecules (SPMs) halt the transition to chronic pathogenic inflammation. We aimed to quantify serum levels of pro- and anti-inflammatory bioactive lipids in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients, and to identify potential relationships with innate responses and clinical outcome. METHODS: Serum from 50 hospital admitted inpatients (22 female, 28 male) with confirmed symptomatic SARS-CoV-2 infection and 94 age- and sex-matched controls collected prior to the pandemic (SARS-CoV-2 negative), were processed for quantification of bioactive lipids and anti-nucleocapsid and anti-spike quantitative binding assays. RESULTS: SARS-CoV-2 serum had significantly higher concentrations of omega-6-derived proinflammatory lipids and omega-6- and omega-3-derived SPMs, compared to the age- and sex-matched SARS-CoV-2-negative group, which were not markedly altered by age or sex. There were significant positive correlations between SPMs, proinflammatory bioactive lipids, and anti-spike antibody binding. Levels of some SPMs were significantly higher in patients with an anti-spike antibody value >0.5. Levels of linoleic acid and 5,6-dihydroxy-8Z,11Z,14Z-eicosatrienoic acid were significantly lower in SARS-CoV-2 patients who died. CONCLUSIONS: SARS-CoV-2 infection was associated with increased levels of SPMs and other pro- and anti-inflammatory bioactive lipids, supporting the future investigation of the underlying enzymatic pathways, which may inform the development of novel treatments.

Clinical and Preclinical Evidence for Roles of Soluble Epoxide Hydrolase in Osteoarthritis Knee Pain.

OBJECTIVE: Chronic pain due to osteoarthritis (OA) is a major clinical problem, and existing analgesics often have limited beneficial effects and/or adverse effects, necessitating the development of novel therapies. Epoxyeicosatrienoic acids (EETs) are endogenous antiinflammatory mediators, rapidly metabolized by soluble epoxide hydrolase (EH) to dihydroxyeicosatrienoic acids (DHETs). We undertook this study to assess whether soluble EH-driven metabolism of EETs to DHETs plays a critical role in chronic joint pain associated with OA and provides a new target for treatment. METHODS: Potential associations of chronic knee pain with single-nucleotide polymorphisms (SNPs) in the gene-encoding soluble EH and with circulating levels of EETs and DHETs were investigated in human subjects. A surgically induced murine model of OA was used to determine the effects of both acute and chronic selective inhibition of soluble EH by N-[1-(1-oxopropy)-4-piperidinyl]-N'-(trifluoromethoxy)phenyl]-urea (TPPU) on weight-bearing asymmetry, hind paw withdrawal thresholds, joint histology, and circulating concentrations of EETs and DHETs. RESULTS: In human subjects with chronic knee pain, 3 pain measures were associated with SNPs of the soluble EH gene EPHX2, and in 2 separate cohorts of subjects, circulating levels of EETs and DHETs were also associated with 3 pain measures. In the murine OA model, systemic administration of TPPU both acutely and chronically reversed established pain behaviors and decreased circulating levels of 8,9-DHET and 14,15-DHET. EET levels were unchanged by TPPU administration. CONCLUSION: Our novel findings support a role of soluble EH in OA pain and suggest that inhibition of soluble EH and protection of endogenous EETs from catabolism represents a potential new therapeutic target for OA pain.

The prevalence and distribution of the variants of Gantzer's muscle: a meta-analysis of cadaveric studies.

The Gantzer's muscle is often present in the flexor compartment of the forearm. It lies underneath flexor digitorum superficialis and compresses the anterior interosseous nerve. Furthermore, this muscle frequently bestows an accessory muscle of flexor pollicis longus or flexor digitorum profundus, or sometimes together. The current meta-analysis aims to compute the prevalence of subtypes of Gantzer's muscle. Major electronic databases (PubMed, Scopus, Google Scholar, etc.) were searched for title and abstract. After removing the duplicate citations, the titles/abstracts were shortlisted with the help of inclusion and exclusion criteria. The shortlisted titles/abstracts were downloaded or collected from the library. The data of all subtypes of Gantzer's muscle were pooled from shortlisted published manuscripts for meta-analysis. The pooled estimate of other anatomical characteristics was also observed. A total of 59 cadaveric studies of sample size 5,903 were evaluated for pooled prevalence of flexor pollicis longus (accessory head). Similarly, the authors evaluated 14 studies of 1,627 upper limbs for flexor digitorum profundus (accessory head). The unit of analysis was per 100 upper limbs. The Pooled prevalence of accessory muscle of flexor pollicis longus and flexor digitorum profundus were 48% (95% CI, 44%-52%) and 17% (95% CI, 13%-21%), respectively. The Gantzer's muscle is present in 2/3rd of the upper limbs. Accessory head of flexor pollicis longus is almost three times more common than the accessory head of flexor digitorum profundus. A classification of Gantzer's muscle is needed to reduce the ignorance of these variants.