Safety and efficacy of intra-erythrocyte dexamethasone sodium phosphate in children with ataxia telangiectasia (ATTeST): a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Ataxia telangiectasia is a multisystem disorder with progressive neurodegeneration. Corticosteroids can improve neurological functioning in patients with the disorder but adrenal suppression and symptom recurrence on treatment discontinuation has limited their use, prompting the development of novel steroid delivery systems. The aim of the ATTeST study was to evaluate the efficacy and safety of intra-erythrocyte delivery of dexamethasone sodium phosphate compared with placebo in children with ataxia telangiectasia. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 trial was done at 22 centres in 12 countries (Australia, Belgium, Germany, India, Israel, Italy, Norway, Poland, Spain, Tunisia, the UK, and the USA). Eligible participants were children aged 6 years or older weighing more than 15 kg who met clinical criteria for ataxia telangiectasia but who had preserved autonomous gait. Participants were randomly assigned (1:1:1) to low-dose (approximately 5-10 mg), or high-dose (approximately 14-22 mg) intra-erythrocyte dexamethasone sodium phosphate, or placebo, using an independent interactive web response system, with minimisation for sex and age (6-9 years vs ≥10 years). Intravenous intra-erythrocyte dexamethasone sodium phosphate was administered once a month for 6 months. Participants, employees of the sponsor, investigators, all raters of efficacy endpoints, and central reviewers were masked to treatment assignment and dose allocations. The primary efficacy endpoint was change in the modified International Cooperative Ataxia Rating Scale (mICARS) from baseline to month 6, assessed in the modified intention-to-treat (mITT) population, which included all randomly assigned participants who received at least one dose of study drug and had at least one post-baseline efficacy assessment. This trial is registered with Clinicaltrials.gov (NCT02770807) and is complete. FINDINGS: Between March 2, 2017, and May 13, 2021, 239 children were assessed for eligibility, of whom 176 were randomly assigned. One patient assigned to high-dose intra-erythrocyte dexamethasone sodium phosphate did not initiate treatment. 175 patients received at least one dose of treatment (59 patients received the low dose and 57 received the high dose of intra-erythrocyte dexamethasone sodium phosphate, and 59 received placebo). The mITT population comprised 164 participants (56 children in the low-dose group, 54 children in the high-dose group, and 54 in the placebo group). Compared with the placebo group, no differences were identified with regard to change in mICARS score from baseline to 6 months in the low-dose group (least squares mean difference -1·37 [95% CI -2·932 to 0·190]) or the high-dose group (-1·40 [-2·957 to 0·152]; p=0·0765). Adverse events were reported in 43 (73%) of 59 participants in the low-dose group, 47 (82%) of 57 participants in the high-dose group, and 43 (73%) of 59 participants in the placebo group. Serious adverse events were observed in six (10%) of 59 participants in the low-dose group, seven (12%) of 57 participants in the high-dose group, and seven (12%) of 59 participants in the placebo group. There were no reports of hyperglycaemia, hypertension, hirsutism, or Cushingoid appearance in any of the treatment groups, nor any treatment-related deaths. INTERPRETATION: Although there were no safety concerns, the primary efficacy endpoint was not met, possibly related to delays in treatment reducing the number of participants who received treatment as outlined in the protocol, and potentially different treatment effects according to age. Studies of intra-erythrocyte delivery of dexamethasone sodium phosphate will continue in participants aged 6-9 years, on the basis of findings from subgroup analyses from this trial. FUNDING: EryDel and Quince Therapeutics.

A Database Tool Integrating Genomic and Pharmacologic Data from Adrenocortical Carcinoma (ACC) Cell Lines, PDX, and Patient Samples.

Adrenocortical carcinoma (ACC) is a rare and highly heterogeneous disease with a notably poor prognosis due to significant challenges in diagnosis and treatment. Emphasising on the importance of precision medicine, there is an increasing need for comprehensive genomic resources alongside well-developed experimental models to devise personalized therapeutic strategies. We present ACC_CellMinerCDB, a substantive genomic and drug sensitivity database (available at https://discover.nci.nih.gov/acc_cellminercdb) comprising ACC cell lines, patient-derived xenografts, surgical samples, combined with responses to over 2,400 drugs examined by NCI and NCATS. This database exposes shared genomic pathways among ACC cell lines and surgical samples, thus authenticating the cell lines as research models. It also allows exploration of pertinent treatment markers such as MDR-1, SOAT1, MGMT, MMR and SLFN11, and introduces the potential to repurpose agents like temozolomide for ACC therapy. ACC_CellMinerCDB provides the foundation for exploring larger preclinical ACC models.

Protective effect of rutin on acrylamide induced ovarian inflammation, oxidative stress, DNA damage, and hormonal changes: Based on in silico and in vivo study.

Acrylamide (AA) is a carcinogenic compound that affects people due to its frequent use in laboratories and industry as well as the high-temperature cooking of foods with high hydrocarbon content. AA is known to cause severe reproductive abnormalities. The main aim of this study is to evaluate the protective effect of rutin (RU), a phytoactive compound, against AA-induced reproductive toxicity in female rats. Initially, rats were exposed to AA (40 mg/kg for 10 days). Therapy of RU was given after AA intoxication consecutively for 3 days. After 24 h of the last treatment, all the animals were sacrificed. The study evaluated reproductive hormones, oxidative stress markers, membrane-bound enzymes, DNA damage, histological findings, and an in silico approach to determine the protective efficacy of RU. The results indicated that RU significantly protected against inflammation, oxidative stress, and DNA damage induced by AA, likely due to its antioxidant properties.

Effectiveness of low to moderate potency topical corticosteroids for phimosis resolution in children: results of a network meta-analysis.

PURPOSE: The use of topical corticosteroids (TCSs) has become an efficient, less-invasive treatment for phimosis. Whether any significant difference in efficacy exists between TCSs based on their potency is unclear. METHODS: Electronic databases were searched up to March 2024 for randomised controlled trials (RCTs) comparing the use of any type or concentration of TCSs with placebo or no treatment in boys with any degree of physician diagnosed phimosis. A random-effects network meta-analysis (NMA) using a consistency model within a frequentist approach was employed. The primary outcome was partial or complete resolution of phimosis reported as a pooled risk ratio (RR) with 95% CI. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities. RESULTS: Seventeen RCTs, containing 2057 participants were identified. NMA suggested that, compared with control, the high (RR 3.19 (95% CI 1.42 to 7.16), moderate (RR 2.68 (95% CI 1.87 to 3.83) and low (RR 3.05 (95% CI 1.63 to 5.71) potency TCSs statistically significantly increased complete or partial clinical resolution of phimosis. The SUCRA plot revealed that high potency (SUCRA = 0.76) was ranked first followed by low and moderate TCSs. When we assessed comparative efficacy among TCSs based on potency, none of the classes were superior to others. The certainty of the evidence for an effect of moderate potent TCSs was that of moderate GRADE quality. CONCLUSION: Moderate to low potency TCSs are of comparable therapeutic effect in the treatment of phimosis to that of highly potent formulations. More high-quality RCTs are warranted.

Assessment of the Inhibitory Efficacy of a Thiazole Derivative as an Efficient Corrosion Inhibitor for Augmenting the Resistance of MS in Acidic Environments.

Numerous thiazole compounds have been developed as cutting-edge inhibitors because of a rising fascination with using corrosion inhibitors (CIs) and preventative measures to prevent mild steel (MS) from deteriorating. In this study, the ability of a novel thiazole derivative, 2-hydrazono-3-methyl-2,3-dihydrobenzo[d]thiazole hydrochloride (HMDBT), to prevent corrosion of MS (MS) in HCl has been reconnoitered using various approaches, Viz. gravimetric analysis, electrochemical (EC) analysis, and different surface characterizations. With an inhibition efficiency (IE %) of 95.35%, the outcomes elucidate that HMDBT functions as a potent MS CI that is environmentally friendly and sustainable. The computed activation and thermodynamic factors were also employed to better explain the process underpinning the inhibiting tendency of HMDBT. According to the computed values, the HMDBT molecules physically and chemically adhered to the MS surface following the Langmuir model, generating a dense protective layer that may be associated with the presence of a benzene ring and heteroatoms (S & N) in the HMDBT architecture. Based on the findings of the EIS studies, an intensification in the CI's concentration from (50 →800) ppm is ushered by increases in polarization resistance (Rp) from (80.72, 354.31) Ω cm2, and attenuation in double-layer capacitance (Cdl) from (198.78 → 44.13) µF cm-2, respectively, confirming the inhibitory proficiency of HMDBT. The IE of the inhibitor was reported around 95.35% by weight loss measurement and 89.94% through EC measurement. Theoretical analysis including density functional theory (DFT) and molecular dynamics (MD) simulations were carried out to investigate the additional effects of HMDBT on the anticorrosion effectiveness and mechanism of inhibition. The theoretical parameters that were calculated provided important assistance in comprehending the inhibitory mechanism that the CI's moieties disclosed and are in strong concord with experimental methods. To create a "green" inhibitor system, the work presented here provided a potent technique to reduce corrosion by adding a potent new inhibitor.

Pulmonary cryptococcosis in chronic kidney disease.

Pulmonary cryptococcosis is a fungal infection caused by Cryptococcus species, with Cryptococcus neoformans being the most common agent, affecting the lungs. While it commonly occurs in immunocompromised individuals, such as those with HIV/AIDS or undergoing immunosuppressive therapy, its presentation in patients with chronic kidney disease (CKD) is relatively rare. However, it should be considered in the differential diagnosis of respiratory infections in patients with CKD, particularly in the context of immunosuppression.

Role of tourniquet release timing on blood loss and functional outcomes in total knee arthroplasty: Insights from a low- and middle-income country.

Purpose: To identify the effect of releasing a tourniquet before versus after wound closure in total knee arthroplasty (TKA) on blood loss, functional outcome and postoperative complications. Methodology: A prospective cohort study was conducted including 53 patients from May 2023 to September 2023. All patients underwent unilateral TKA and were divided into two groups based on surgeon preference of deflating tourniquet, Group A consisted of patients in whom the tourniquet was deflated before wound closure for haemostasis and Group B consisted of patients in which tourniquet was deflated after wound closure and compressive dressing. Blood loss was evaluated via intraoperative blood loss (the number of soaked sponges/gauzes, blood in a suction bottle, total output in a suction bottle-irrigation used) and on-field blood loss and calculated blood loss (Using Gross and Meunier's formula). The Functional outcome was evaluated using Knee injury and osteoarthritis score-42 questions. Early postoperative complications and differences in the requirement of blood transfusions were also assessed. Results: There was a significant difference in intraoperative blood loss between the two groups. The median intraoperative blood loss was 135 mL (interquartile range [IQR]: 90-149) in Group A and 56.2 mL (IQR: 45-68) in Group B (p value: 0.001). However, no difference was found between the groups in calculated blood loss using Gross and Meunier's formula. The median calculated blood loss was 439 mL (IQR: 450-813) in Group A and 508 mL (IQR: 226-671) in group B (p value: 0.981). There was no significant difference between the groups in blood transfusion requirements or functional outcomes. Conclusion: Based on our results, we conclude that the intraoperative blood loss in TKA is significantly different between the groups but only represents a fraction of true blood loss (23%). The timing of releasing the tourniquet does not affect functional outcomes, blood transfusion and postoperative morbidity; hence, any time can be opted as per surgeon preference. Level of Evidence: Level II, prospective comparative study.

Evaluation of antibacterial, antioxidant, and anti-inflammatory properties of GC/MS analysis of extracts of Ajuga. integrifolia Buch.-Ham. leaves.

The purpose of the current study was to examine chemical composition, antioxidant, anti-inflammatory and antibacterial properties of leaves extract of Ajuga integrifolia Buch.-Ham. The antibacterial and antioxidant properties of three different solvents i.e. methanol (AIM), hexane (AIH), and water (AIW) were tested against two bacterial strains Staphylococcus aureus and Escherichia coli. The presence of antioxidant and antibacterial chemicals, such as hexanedioic acid, hexadecanoic acid, nonadecadiene, hexadecen-1-ol, octadecadienoic acid, nonane, phytol, henicosanal, stearyl aldehyde, and neophytadiene, were depicted in the GCMS chromatograms of three extracts. After the extracts' FTIR peaks were examined, it was discovered that phenols, amines, hydroxy groups, and components linked to amino acids were present. Compared to the Hexane and Water extracts, the Methanol extract showed a greater phenolic (196.16 ± 0.0083 mg gallic acid equivalent/gram), flavonoid (222.77 ± 0.002 mg rutin equivalents/g) and phosphomolybdate assay for total antioxidant activity (557.62 ± 0.0023 mg AAE/g). Methanol extract showed the highest scavenging activity with a minimum IC50 value was observed in DPPH assay. AIM showed its maximum anti-denaturation activity i.e. 3.75 ± 0.28%. For antibacterial activities, best zone of inhibition (ZOI) and minimum inhibitory concentration (MIC) was observed in case of the methanol extract as compared to other extracts against methicillin-resistant Staphylococcus aureus and ß-lactam-resistant Escherichia coli.

Microenvironment shapes small-cell lung cancer neuroendocrine states and presents therapeutic opportunities.

Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the cell-extrinsic drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the TME exhibit substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAFs) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Our work provides a comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLC's adaptable nature, opening possibilities for reprogramming the TME-tumor communications that shape SCLC tumor states.

Evaluation of the Efficacy and Safety of Intravenous Immunoglobulin (IVIG) in Moderate-to-Severe Hospitalized COVID-19 Patients: A Randomized, Open-Label Parallel-Group Study.

Purpose: Since February 2020, the world has been overwhelmed by the SARS-CoV-2 outbreak, and several patients suffered interstitial pneumonia and respiratory failure requiring mechanical ventilation, threatening the capability of healthcare systems to handle this amount of critical cases. Intravenous immunoglobulins (IVIG) possess potential immunomodulatory properties beneficial for COVID-19 patients, yet evidence supporting IVIG as adjunctive therapy remains sparse. This study evaluated the outcomes of adjunctive IVIG with the standard of care (SoC) in moderate-to-severe COVID-19 patients. Methods: This randomized study included 59 moderate-to-severe COVID-19 patients with known comorbidities. One arm (n = 33) received high-dose IVIG (400 mg/kg/day) within 48 hours for five days alongside SoC, while the other arm (n = 26) received SoC, comprising steroids, enoxaparin, and remdesivir. The primary endpoint was clinical improvement, as measured by the National Early Warning Score 2 (NEWS2) and discharged/death proportions. Secondary outcomes included IVIG safety, hospitalization duration, changes in oxygen saturation, inflammatory markers, IgG titer, CTSS (CT severity score), and radiological findings. Results: There was an improvement in the NEWS2 at the end of treatment in the IVIG arm (5.67 vs. 5.96). A significant absolute effect improvement (Day 1 vs. Day 9) was seen in serum LDH, D-dimer, hs-CRP, IL-6, CTSS, procalcitonin, respiratory rate, and chest radiographic findings. SARS-CoV-2 IgG titer increased significantly in the IVIG arm. There was a statistically significant reduction in mortality in the IVIG group (5 vs. 10). Conclusion: IVIG was a safe and effective adjunctive therapy to SoC treatment in moderate-to-severe COVID-19 patients needing ventilatory support. Furthermore, studies are required to validate our findings. This trial is registered with CTRI/2021/05/033622.

Endobronchial Inflammatory Myofibroblastic Tumour Masquerading as a Ruptured Hydatid Cyst.

Inflammatory myofibroblastic tumours (IMTs) represent a rare group of neoplastic lesions characterized by a diverse clinical presentation. Endobronchial involvement is infrequently reported, and its manifestation mimicking the symptoms of a ruptured hydatid cyst adds an additional layer of complexity to the diagnostic challenge. This case report delves into an exceptional clinical scenario where an endobronchial IMT masqueraded as a ruptured hydatid cyst, initially confounding the diagnostic team. Through a detailed examination of the patient's clinical history, radiological imaging, bronchoscopy findings and subsequent histopathological analysis, we aim to contribute to the existing medical literature and shed light on the nuances encountered in accurately identifying and differentiating these two entities.

Glaucoma Drug Prescription Pattern in North India: Public vs Private Sector Hospitals.

Background: Glaucoma is an optic neuropathy associated with characteristic structural damage to the optic nerve and associated visual dysfunction that may be caused by various pathological processes. A number of pharmacological agents are used to reduce the intraocular pressure (IOP), involving the usage of two or three medications concurrently. Literature is sparse regarding prescription patterns of antiglaucoma drugs, especially regarding variability in public sector vs private sector hospitals. Drug utilization studies can add insight for crafting rational, affordable, and ocular surface friendly prescriptions. Aim: This study assessed the prescription pattern in glaucoma patients of a public sector, tertiary care hospital vs a private sector tertiary care hospital. Materials and methods: In this retrospective study, pertinent data of diagnosed and labeled glaucoma patients were reviewed. Data collected included demographic details, type of glaucoma, number and nature of drugs prescribed, whether innovator or generic drugs were prescribed, if fixed-drug combinations (FDCs) and preservative-free formulations were prescribed. The prescription patterns between the two sectors were compared, as were the prescription patterns between primary open-angle glaucoma (POAG) and primary angle-closure disease (PACD). Results: A total of 336 prescriptions were evaluated (216 from public sector, group I; 120 from private sector, group II). Travoprost 0.004% was the most prescribed antiglaucoma medication in both group I (30.09%) and group II (38.33%). Brimonidine and brinzolamide (14.17%) was the most prescribed combination in group II, while Brimonidine with Timolol (7.87%) in group I. In group I, Timolol and Travoprost were the most prescribed medications for both PACD and POAG. Conclusion: This study showed that both public sector as well as private sector tertiary care centers prescribe antiglaucoma medications in tune with current principles of rational drug use. Preservative-free drugs were preferred in both the groups for better adherence. How to cite this article: Bhartiya S, Ichhpujani P, Parmar UPS, et al.Glaucoma Drug Prescription Pattern in North India: Public vs Private Sector Hospitals. J Curr Glaucoma Pract 2024;18(1):16-22.

Comparative miRNome and transcriptome analyses reveal the expression of novel miRNAs in the panicle of rice implicated in sustained agronomic performance under terminal drought stress.

MAIN CONCLUSION: Differential expression of 128 known and 111 novel miRNAs in the panicle of Nagina 22 under terminal drought stress targeting transcription factors, stress-associated genes, etc., enhances drought tolerance and helps sustain agronomic performance under terminal drought stress. Drought tolerance is a complex multigenic trait, wherein the genes are fine-tuned by coding and non-coding components in mitigating deleterious effects. MicroRNA (miRNA) controls gene expression at post-transcriptional level either by cleaving mRNA (transcript) or by suppressing its translation. miRNAs are known to control developmental processes and abiotic stress tolerance in plants. To identify terminal drought-responsive novel miRNA in contrasting rice cultivars, we constructed small RNA (sRNA) libraries from immature panicles of drought-tolerant rice [Nagina 22 (N 22)] and drought-sensitive (IR 64) cultivars grown under control and terminal drought stress. Our analysis of sRNA-seq data resulted in the identification of 169 known and 148 novel miRNAs in the rice cultivars. Among the novel miRNAs, 68 were up-regulated while 43 were down-regulated in the panicle of N 22 under stress. Interestingly, 31 novel miRNAs up-regulated in N 22 were down-regulated in IR 64, whereas 4 miRNAs down-regulated in N 22 were up-regulated in IR 64 under stress. To detect the effects of miRNA on mRNA expression level, transcriptome analysis was performed, while differential expression of miRNAs and their target genes was validated by RT-qPCR. Targets of the differentially expressed miRNAs include transcription factors and stress-associated genes involved in cellular/metabolic/developmental processes, response to abiotic stress, programmed cell death, photosynthesis, panicle/seed development, and grain yield. Differential expression of the miRNAs could be validated in an independent set of the samples. The findings might be useful in genetic improvement of drought-tolerant rice.

Review of nano-based smart coatings for corrosion mitigation: mechanisms, performance, and future prospects.

In response to environmental concerns about toxic corrosion inhibitors, nanomaterials have gained attention for their enhanced corrosion inhibition properties due to their high surface-to-volume ratio. This paper summarizes advancements in utilizing nanomaterials to control corrosion, exploring various preparation methods and effectiveness as inhibitors. Nano-based intelligent coatings have emerged as promising solutions, with this review examining their corrosion inhibition mechanisms, performance attributes, and future prospects. By combining nanomaterials with traditional inhibitors, synergistic effects can be achieved. Performance assessment extends to real-world scenarios, considering factors like adhesion, durability, and practical implementation across industries. Future trends include integrating real-time monitoring abilities and using environmentally conscious nanomaterials for sustainable corrosion control.

Catalytic synergy of WS2-anchored PdSe2 for highly sensitive hydrogen gas sensor.

Hydrogen (H2) is widely used in industrial processes and is one of the well-known choices for storage of renewable energy. H2 detection has become crucial for safety in manufacturing, storage, and transportation due to its strong explosivity. To overcome the issue of explosion, there is a need for highly selective and sensitive H2 sensors that can function at low temperatures. In this research, we have adequately fabricated an unreported van der Waals (vdWs) PdSe2/WS2 heterostructure, which exhibits exceptional properties as a H2 sensor. The formation of these heterostructure devices involves the direct selenization process using chemical vapor deposition (CVD) of Pd films that have been deposited on the substrate of SiO2/Si by DC sputtering, followed by drop casting of WS2 nanoparticles prepared by a hydrothermal method onto device substrates including pre-patterned electrodes. The confirmation of the heterostructure has been done through the utilization of powder X-ray diffraction (XRD), depth-dependent X-ray photoelectron spectroscopy (XPS) and field-emission scanning electron microscopy (FE-SEM) techniques. Also, the average roughness of thin films is decided by Atomic Force Microscopy (AFM). The comprehensive research shows that the PdSe2/WS2 heterostructure-based sensor produces a response that is equivalent to 67.4% towards 50 ppm H2 at 100 °C. The response could be a result of the heterostructure effect and the superior selectivity for H2 gas in contrast to other gases, including NO2, CH4, CO and CO2, suggesting tremendous potential for H2 detection. Significantly, the sensor exhibits fast response and a recovery time of 31.5 s and 136.6 s, respectively. Moreover, the explanation of the improvement in gas sensitivity was suggested by exploiting the energy band positioning of the PdSe2/WS2 heterostructure, along with a detailed study of variations in the surface potential. This study has the potential to provide a road map for the advancement of gas sensors utilizing two-dimensional (2D) vdWs heterostructures, which exhibit superior performance at low temperatures.

Are We Providing Enough Information to the Pathologists? An Audit of Filling of Histopathology Request Forms for Surgically Resected Tumours.

OBJECTIVE: To analyse quantitatively the adequacy of demographics of clinical information and highlight specific areas of neglect, by assessing the adequacy of filling out histopathology request forms. STUDY DESIGN: Clinical Audit. Place and Duration of the Study: Department of Pathology, Dow University of Health Sciences (DUHS), Karachi, Pakistan, from January to September 2021. METHODOLOGY: A retrospective audit was carried out on the request forms of surgically resected tumours and biopsies. The recorded details of the patients' demographics and biopsy, clinical history and examination, and intraoperative findings were analysed. RESULTS: Out of 175 forms, patients' names were written in 174 (99.4%) while medical record numbers were written in 113 (64.6%). The doctors' names were given in 172 (98.3%) forms and phone numbers in 34 (19.4%). A clinical diagnosis was provided in 164 (93.7%) forms, while 152 (86.9%) forms correctly entered the biopsy site. Sixty-seven (38.3%) forms included the correct nature of the biopsy. Relevant operative details were provided in half of the forms. Symptoms and their duration were mentioned in 144 (82.3%) and 100 (57.1%), respectively. The form-filling rate was the same for both benign and malignant tumours. CONCLUSION: This study shows that in a significant proportion of cases, complete relevant information is not provided to the histopathologists on request forms for logistics. KEY WORDS: Histopathology, Request forms, Tumours, Audit.

Efficacy of Bilateral Erector Spinae Block in Patients Undergoing Posterior Spine Fusion Surgeries: A Comparative Randomised Controlled Trial.

Introduction During spine surgeries, various levels of tissue injury can result in varying hemodynamic responses and significant postoperative pain. Perioperative pain management is essential to controlling hemodynamic responses and postoperative pain management. Erector spinae plane (ESP) blocks can help alleviate this pain by blocking the dorsal rami of the spinal nerve. This study aims to evaluate the efficacy of ESP by assessing the perioperative opioid requirement, hemodynamic parameters, and visual analogue score (VAS) during the postoperative period. Methods In this study, 56 patients underwent elective posterior spine fusion surgeries under conventional anaesthesia and were allocated into two groups: 28 patients were included in the conventional group (Group C) and 28 patients in the ESP group (Group E). Group C patients received 20 ml of 0.9% sodium chloride (NaCl) on each side, and Group E patients received 20 ml of 0.25% bupivacaine + 4 mg dexamethasone on each side under ultrasound sonography guidance. Postoperative pain was assessed using the VAS score. The hemodynamic parameters during the intraoperative period, the time for the first opioid analgesia requirement until 24 hours in the postoperative period, and the amount of cumulative opioid consumption during the perioperative period were observed. Results Postoperative VAS was lower in Group E (P < 0.001). There were significant differences in hemodynamic parameters: heart rate (P < 0.045), systolic blood pressure (P < 0.002), diastolic blood pressure (P < 0.003), and mean arterial pressure (P < 0.002) at the time of incision in Group E. Intraoperative opioid requirements at the time of incision (P < 0.036), 60th minutes (P < 0.023), 120th minutes (P < 0.023), and postoperative opioid requirements at the first hour (P < 0.001), sixth hour (P < 0.004), 14th hour (P < 0.025), 20th hour (P < 0.009), and 24th hour (P < 0.025) had lower opioid requirements in Group E than Group C. Conclusion ESP block is a more site-specific dorsal rami block with a better perioperative hemodynamic profile, a part of multimodal analgesia intraoperatively, and excellent postoperative analgesia with fewer postoperative opioid requirements in multilevel spine fusion surgeries.

Epigenetic Modifications in Genome Help Remembering the Stress Tolerance Strategy Adopted by the Plant.

Genetic information in eukaryotic organisms is stored, replicated, transcribed, and inherited through the nucleus of a cell. Epigenetic modifications in the genetic material, including DNA methylation, histone modification, changes in non-coding RNA (ncRNA) biogenesis, and chromatin architecture play important roles in determining the genomic landscape and regulating gene expression. Genome architecture (structural features of chromatin, affected by epigenetic modifications) is a major driver of genomic functions/activities. Segregation of euchromatin (transcriptionally active) from heterochromatin (transcriptionally repressed chromosome) and positioning of genes in specific nuclear space in eukaryotic cells emphasise non-randomness in the organization of the genetic information. Not only does the base sequence of a gene carry the genetic information but the covalent modifications of bases, three-dimensional positioning of the genome, and chromatin loops are vital for switching on/off the gene and regulating its expression during growth/environmental stress. The epigenetic dynamics depend on the activities of writers and erasers under changing environmental conditions. The discovery of non-coding RNAs (one of the players in de novo methylation of DNA), increased DNA methylation protein (guide for the DNA demethylase), and methylation monitoring sequence (that helps keep a balance between DNA demethylation and methylation) have been some of the new developments in the era of epigenomics. To respond to environmental stimuli, plants depend on modulating gene expression through different mechanisms including biochemical, molecular, genetic, and epigenetic alterations. Studies on plants might provide better insights into epigenetic stress memory and molecular bases of adaptability to enable (epi)genome editing of crops for climate resilience and sustainable agriculture in the present era of multifaceted climate change.