Transcriptome analysis of apical meristem enriched bud samples for size dependent flowering commitment in Crocus sativus reveal role of sugar and auxin signalling.

BACKGROUND: Cultivation of Crocus sativus (saffron) faces challenges due to inconsistent flowering patterns and variations in yield. Flowering takes place in a graded way with smaller corms unable to produce flowers. Enhancing the productivity requires a comprehensive understanding of the underlying genetic mechanisms that govern this size-based flowering initiation and commitment. Therefore, samples enriched with non-flowering and flowering apical buds from small (< 6 g) and large (> 14 g) corms were sequenced. METHODS AND RESULTS: Apical bud enriched samples from small and large corms were collected immediately after dormancy break in July. RNA sequencing was performed using Illumina Novaseq 6000 to access the gene expression profiles associated with size dependent flowering. De novo transcriptome assembly and analysis using flowering committed buds from large corms at post-dormancy and their comparison with vegetative shoot primordia from small corms pointed out the major role of starch and sucrose metabolism, Auxin and ABA hormonal regulation. Many genes with known dual responses in flowering development and circadian rhythm like Flowering locus T and Cryptochrome 1 along with a transcript showing homology with small auxin upregulated RNA (SAUR) exhibited induced expression in flowering buds. Thorough prediction of Crocus sativus non-coding RNA repertoire has been carried out for the first time. Enolase was found to be acting as a major hub with protein-protein interaction analysis using Arabidopsis counterparts. CONCLUSION: Transcripts belong to key pathways including phenylpropanoid biosynthesis, hormone signaling and carbon metabolism were found significantly modulated. KEGG assessment and protein-protein interaction analysis confirm the expression data. Findings unravel the genetic determinants driving the size dependent flowering in Crocus sativus.

Long-Term Safety Analysis of the BBV152 Coronavirus Vaccine in Adolescents and Adults: Findings from a 1-Year Prospective Study in North India.

BACKGROUND AND OBJECTIVE: Evidence on the long-term safety of COVID-19 vaccines is scarce. Here, in continuation of our previously published results on short-term safety, we provide data on the long-term safety of the BBV152 vaccine in adolescents and adults. METHODS: This was a prospective observational study conducted from January 2022 to August 2023. Adolescents and adults receiving the BBV152 vaccine were interviewed telephonically about long-term adverse events of special interest (AESIs) after 1 year of vaccination. Risk factors of AESIs and AESIs persistent for at least 1 month were identified. RESULTS: Out of 1024 individuals enrolled, 635 adolescents and 291 adults could be contacted during the 1-year follow-up. Viral upper respiratory tract infections were reported by 304 (47.9%) adolescents and 124 (42.6%) adults in this period. New-onset skin and subcutaneous disorders (10.5%), general disorders (10.2%), and nervous system disorders (4.7%) were the common AESIs in adolescents. General disorders (8.9%), musculoskeletal disorders (5.8%), and nervous system disorders (5.5%) were the common AESIs in adults. Menstrual abnormalities were noticed in 4.6% of female participants. Ocular abnormalities and hypothyroidism were observed in 2.7% and 0.6% of participants, respectively. Among serious AESIs (1%), stroke and Guillain-Barre syndrome were identified in 0.3% and 0.1% of participants, respectively. Among adolescents, female individuals, those with a history of allergy and post-vaccination typhoid were respectively at 1.6, 2.8, and 2.8 times higher risk of AESIs. The majority of the AESIs persisted at the 1-year follow-up. Female individuals, adolescents with pre-vaccination COVID-19, those with co-morbidities, and those with post-vaccination typhoid had respectively 1.6, 2, 2.7, and 3.2 times higher odds of persistent AESIs. Adults with co-morbidities had more than 2 times higher odds of AESIs and persistent AESIs. CONCLUSIONS: The patterns of AESIs developing after BBV152 differed from those reported with other COVID-19 vaccines as well as between adolescents and adults. With the majority of AESIs persisting for a significant period, extended surveillance of COVID-19-vaccinated individuals is warranted to understand the course and outcomes of late-onset AESIs. Serious AESIs might not be uncommon and necessitate enhanced awareness and larger studies to understand the incidence of immune-mediated phenomena post-COVID-19 vaccination. The relationship of AESIs with sex, co-morbidities, pre-vaccination COVID-19, and non-COVID illnesses should be explored in future studies.

Opioid-free anesthesia using a combination of ketamine and dexmedetomidine in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial.

BACKGROUND: Opioids administered as bolus doses or continuous infusions are widely used for major and daycare surgeries. Opioid-free anesthesia is multimodal anesthesia and analgesia that does not use opioids, benefiting patients from opioid-related adverse effects. We compared the postoperative analgesic requirements of patients scheduled for elective laparoscopic cholecystectomy under opioid-free and opioid-based anesthesia. METHODS: Study included 88 patients aged 18-60 years with American Society of Anesthesiologists physical status 1 and 2 who underwent elective laparoscopic cholecystectomy. Participants were randomly divided into two groups with 44 in each. The opioid-free group was administered an intravenous bolus of ketamine and dexmedetomidine, whereas fentanyl was used in opioid group. Primary outcome was to compare the total amount of fentanyl consumed by both groups during 6 h postoperative period. Episodes of postoperative nausea and vomiting (PONV) and vital signs were noted throughout the postoperative period to analyze the secondary outcomes. RESULTS: Both groups had similar demographic characteristics. The opioid-free group required lesser analgesia within the first 2 h (61.4 ± 17.4 vs. 79.0 ± 19.4 of fentanyl, P < 0.001), which was statistically significant. However, fentanyl consumption was comparable between the groups at 6 h (152 ± 28.2 vs. 164 ± 33.4, P = 0.061). Compared with 4.5% of the participants in the opioid-free group, 34% of those in the opioid-based group developed moderate PONV. CONCLUSIONS: Opioid-free anesthesia in patients undergoing laparoscopic cholecystectomy reduced the requirement of analgesia in first two-hour postoperative period and was associated with decreased PONV.

Comparative evaluation of nebulised dexmedetomidine vs fentanyl for the treatment of post-dural puncture headache (PDPH) in parturients after caesarean section under spinal anaesthesia: A randomised controlled study.

Background and Aims: The incidence of post-dural puncture headache (PDPH) following spinal anaesthesia in the obstetric population is around 0.5%-2%. Hydration, bed rest, caffeine, paracetamol, non-steroid anti-inflammatory drugs, epidural blood patches, etc., are the various modalities used for its management. This study aims to compare nebulised dexmedetomidine versus fentanyl for the treatment of PDPH in parturients after caesarean section under spinal anaesthesia. Methods: Ninety obstetric patients aged 18-35 years with American Society of Anesthesiologists (ASA) physical status II/III and suffering from PDPH as per the criteria of the International Headache Society after caesarean section under spinal anaesthesia were recruited in this double-blinded randomised study. Patients were randomised to Group D (dexmedetomidine 1 µg/kg nebulisation), Group F (fentanyl 1 µg/kg nebulisation), and Group S (saline nebulisation 4mL). The nebulisation was done 12 hourly for 72 hours. Assessment parameters included pain score and the requirement of additional treatment such as paracetamol, caffeine, and epidural blood patch. Analysis of variance test was used for continuous quantitative variables, and the Kruskal-Wallis test was used for quantitative discrete data. Results: The pain scores at 1, 6, 12, 24, 48, and 72 hours following nebulisation were significantly lower in Group D in comparison to groups F and S (P < 0.001). The number of patients requiring additional analgesic therapy was lower in Group D in comparison to patients in other groups (P < 0.001). Conclusion: Dexmedetomidine nebulisation resulted in effective reduction in PDPH symptoms and pain scores. Nebulisation with fentanyl did not alleviate PDPH symptoms when compared to the control group.

The Impact of Topical Application of Platelet-Rich Fibrin on Graft Survival in Surgeries for Chronic Otitis Media.

OBJECTIVE: This study aims to evaluate the efficacy of platelet-rich fibrin (PRF) application in tympanoplasty procedures for patients with chronic otitis media (COM), assessing its influence on graft survival and healing time. METHODS: In this prospective interventional study, conducted between January 2022 and June 2023, 80 patients diagnosed with COM were enrolled and divided into two groups. Group A underwent standard tympanic membrane repair using temporal fascia grafts (TFG), while Group B received TFG with adjunctive PRF application. The patients were observed and assessed over a 20-week postoperative period. RESULTS: The study showed a significant enhancement in graft survival rates in Group B (TFG+PRF), with only one residual perforation compared to seven in Group A (TFG alone) at 20 weeks (p=0.02534). Furthermore, Group B patients experienced faster healing, achieving 97.5% graft integrity at 10 and 20 weeks, in contrast to Group A's 87.5%. CONCLUSION: The application of PRF in tympanoplasty procedures for COM notably enhances graft stability and expedites the healing process. These findings suggest that PRF can be a valuable adjunct in otolaryngological surgeries, offering potential improvements in patient outcomes and surgical efficacy.

Host Response of Arabidopsis thaliana Interaction with Fungal Endophytes Involves microRNAs.

Plant and fungus interaction is a complex process involving many molecular factors determining the nature of relationship. The enigmatic methodology by which fungal endophytes are able to colonise a plant harmoniously is still inexplicable. Small RNAs have been identified as major regulatory elements under various biotic interactions. However, their role in endophytic plant-fungal interactions remain to be elucidated. Therefore, transcript expression data available on Gene Expression Omnibus for Arabidopsis thaliana was utilised for miRNAs identification under endophytism. The analysis predicted 15 miRNAs with differential expression of which the ath-miRNA398b modulation was significant. Application of psRNAtarget, C-mii, pmiREN, and TarDB provided a pool of 357 target genes for these miRNAs. Protein-protein interaction analysis identified major hub proteins, including BTB/POZ domain-containing protein, beta-Xylosidase-2 (AtBXL2), and Copper/Zinc Superoxide Dismutase-2 (AtSOD2). The quantitative real-time PCR validated the computational prediction and expression for selected target genes AtSOD2, AtBXL2, and AtRCA along with ath-miRNA398b under endophytism. Overall, results indicate that miRNAs have a significant role in regulating Arabidopsis thaliana-endophytic fungal interaction.

Akt activation ameliorates deficits in hippocampal-dependent memory and activity-dependent synaptic protein synthesis in an Alzheimer's disease mouse model.

Protein kinase-B (Akt) and the mechanistic target of rapamycin (mTOR) signaling pathways are implicated in Alzheimer's disease (AD) pathology. Akt/mTOR signaling pathways, activated by external inputs, enable new protein synthesis at the synapse and synaptic plasticity. The molecular mechanisms impeding new protein synthesis at the synapse in AD pathogenesis remain elusive. Here, we aimed to understand the molecular mechanisms prior to the manifestation of histopathological hallmarks by characterizing Akt1/mTOR signaling cascades and new protein synthesis in the hippocampus of WT and amyloid precursor protein/presenilin-1 (APP/PS1) male mice. Intriguingly, compared to those in WT mice, we found significant decreases in pAkt1, pGSK3ß, pmTOR, pS6 ribosomal protein, and p4E-BP1 levels in both post nuclear supernatant and synaptosomes isolated from the hippocampus of one-month-old (presymptomatic) APP/PS1 mice. In synaptoneurosomes prepared from the hippocampus of presymptomatic APP/PS1 mice, activity-dependent protein synthesis at the synapse was impaired and this deficit was sustained in young adults. In hippocampal neurons from C57BL/6 mice, downregulation of Akt1 precluded synaptic activity-dependent protein synthesis at the dendrites but not in the soma. In three-month-old APP/PS1 mice, Akt activator (SC79) administration restored deficits in memory recall and activity-dependent synaptic protein synthesis. C57BL/6 mice administered with an Akt inhibitor (MK2206) resulted in memory recall deficits compared to those treated with vehicle. We conclude that dysregulation of Akt1/mTOR and its downstream signaling molecules in the hippocampus contribute to memory recall deficits and loss of activity-dependent synaptic protein synthesis. In AD mice, however, Akt activation ameliorates deficits in memory recall and activity-dependent synaptic protein synthesis.

Glomerular-tubular crosstalk via cold shock Y-box binding protein-1 in the kidney.

Glomerular-tubular crosstalk within the kidney has been proposed, but the paracrine signals enabling this remain largely unknown. The cold-shock protein Y-box binding protein 1 (YBX1) is known to regulate inflammation and kidney diseases but its role in podocytes remains undetermined. Therefore, we analyzed mice with podocyte specific Ybx1 deletion (Ybx1ΔPod). Albuminuria was increased in unchallenged Ybx1ΔPod mice, which surprisingly was associated with reduced glomerular, but enhanced tubular damage. Tubular toll-like receptor 4 (TLR4) expression, node-like receptor protein 3 (NLRP3) inflammasome activation and kidney inflammatory cell infiltrates were all increased in Ybx1ΔPod mice. In vitro, extracellular YBX1 inhibited NLRP3 inflammasome activation in tubular cells. Co-immunoprecipitation, immunohistochemical analyses, microscale cell-free thermophoresis assays, and blunting of the YBX1-mediated TLR4-inhibition by a unique YBX1-derived decapeptide suggests a direct interaction of YBX1 and TLR4. Since YBX1 can be secreted upon post-translational acetylation, we hypothesized that YBX1 secreted from podocytes can inhibit TLR4 signaling in tubular cells. Indeed, mice expressing a non-secreted YBX1 variant specifically in podocytes (Ybx1PodK2A mice) phenocopied Ybx1ΔPod mice, demonstrating a tubular-protective effect of YBX1 secreted from podocytes. Lipopolysaccharide-induced tubular injury was aggravated in Ybx1ΔPod and Ybx1PodK2A mice, indicating a pathophysiological relevance of this glomerular-tubular crosstalk. Thus, our data show that YBX1 is physiologically secreted from podocytes, thereby negatively modulating sterile inflammation in the tubular compartment, apparently by binding to and inhibiting tubular TLR4 signaling. Hence, we have uncovered an YBX1-dependent molecular mechanism of glomerular-tubular crosstalk.

Tissue factor binds to and inhibits interferon-α receptor 1 signaling.

Tissue factor (TF), which is a member of the cytokine receptor family, promotes coagulation and coagulation-dependent inflammation. TF also exerts protective effects through unknown mechanisms. Here, we showed that TF bound to interferon-α receptor 1 (IFNAR1) and antagonized its signaling, preventing spontaneous sterile inflammation and maintaining immune homeostasis. Structural modeling and direct binding studies revealed binding of the TF C-terminal fibronectin III domain to IFNAR1, which restricted the expression of interferon-stimulated genes (ISGs). Podocyte-specific loss of TF in mice (PodΔF3) resulted in sterile renal inflammation, characterized by JAK/STAT signaling, proinflammatory cytokine expression, disrupted immune homeostasis, and glomerulopathy. Inhibiting IFNAR1 signaling or loss of Ifnar1 expression in podocytes attenuated these effects in PodΔF3 mice. As a heteromer, TF and IFNAR1 were both inactive, while dissociation of the TF-IFNAR1 heteromer promoted TF activity and IFNAR1 signaling. These data suggest that the TF-IFNAR1 heteromer is a molecular switch that controls thrombo-inflammation.

Intranasal sphenopalatine ganglion block by lignocaine spray for postdural puncture headache following spinal anesthesia: a randomized clinical trial.

INTRODUCTION: In a randomized clinical study, we investigated the effectiveness of nasal lignocaine spray and swabs in treating postdural puncture headache (PDPH) after spinal anesthesia. MATERIAL AND METHODS: Group S patients received two puffs of lignocaine 10% spray in both nostrils followed by cotton soaked in normal saline, and group B patients received two puffs of saline spray in both nostrils followed by a cotton swab soaked in lignocaine 2%. Patients were assessed before the procedure and 30 minutes, 60 minutes, 2 h, 24 h, 48 h, and 72 h after the procedure for pain relief with the help of a visual analogue scale (VAS). Hemodynamic parameters and adverse effects were also recorded. Normally distributed continuous variables were expressed as mean (95% confidence interval) whereas non-normally distributed variables were expressed as median (IQR). Repeated measures analysis of variance was used to compare the VAS score at different time points between test and control groups. The difference in means between the two groups was compared using the independent sample t -test. The paired t-test was used to compare the changes in clinical and laboratory variables. RESULTS: At each time point, the mean VAS score for pain was substantially different between the two groups. Moreover, until the second hour, the VAS score was significantly lower in group S than in group B. No significant intervention-related adverse effect was observed in either group. CONCLUSIONS: Without any noticeable side effects, lignocaine 10% spray is more successful in treating PDPH after spinal anesthesia, particularly in the first two hours.

Factors Affecting Biochemical and Echocardiographic Indices in Type 2 Diabetes Mellitus Patients Without Overt Symptoms of Heart Failure: A Cross-Sectional Study.

Introduction Diabetes is a known risk factor for heart failure (HF), and HF often manifests as a common cardiovascular event in people with type-2 diabetes mellitus (T2DM). Once HF is present, diabetes presents an especially adverse prognosis for subsequent morbidity and mortality. Brain natriuretic peptide (BNP) and n-terminal ProBNP (NT-proBNP) are used as diagnostic biomarkers for HF that are secreted by the ventricles in response to increased myocardial wall stress. If we could unmask some clinical and routine laboratory parameters affecting BNP and ejection fraction (EF), we can predict impending HF and take measures to prevent it. The current study was conducted to investigate the factors affecting BNP and EF for detecting potential HF in T2DM patients who do not exhibit overt HF symptoms. Materials and methods The present cross-sectional study was performed after obtaining ethical clearance from the Institutional Ethics Committee. T2DM patients consulting the Medicine Outpatient Department (OPD) of BRD Medical College Gorakhpur during a two-month period (from 20 July 2023 to 19 September 2023) with age >40 years and duration of T2DM >10 years. Multistage random sampling was done to recruit study participants, and 308 patients participated in the study. Informed consent was obtained from the recruited participants. The chi-square or Fisher's exact test (whichever was applicable) was used to explore the association between categorical variables. Correlation statistics were calculated using Spearman correlation among the NT-proBNP, EF, and other relevant variables. The Statistical Package for Social Sciences (SPSS) (version 21; IBM SPSS Statistics for Windows, Armonk, NY) was used for the analysis, and a two-sided p-value of < 0.05 was considered significant. Results Three hundred and eight diabetic patients satisfying inclusion and exclusion criteria were enrolled as study participants and completed the study. The mean age of the total study subjects was 60.82 ± 9.23 years. There were 161 (52.3%) male and 147 (47.7%) female participants, and about half (153/308, 49.7%) of the participants belonged to the age group 40-60 years. There was a statistically significant association (p = 0.01) between NT-proBNP and glycated hemoglobin. Statistically highly significant (p < 0.001) associations were found between NT-proBNP with duration of T2DM and EF. There was a strong negative correlation (correlation coefficient = -0.743) between EF and NT-proBNP, and this correlation was statistically highly significant with a p-value < 0.001. Conclusion Elevated NT-proBNP levels and impaired EF were found in a significant proportion of these patients, indicating an increased risk of cardiovascular complications. This study highlights a significant association between NT-proBNP and EF in patients with T2DM in those without overt heart failure symptoms. Furthermore, longer T2DM duration and higher HbA1c levels were found to be associated with elevated NT-proBNP levels, while longer T2DM duration and elevated NT-proBNP were linked to lower EF. These findings have important clinical implications, as they suggest that monitoring NT-proBNP levels in patients with T2DM without clinical features of overt heart failure may help identify those at risk for decreased EF and potentially prevent heart failure.

Study of growth-improving and sporophore-inducing endobacteria isolated from Pleurotus pulmonarius.

Several Pleurotus species (oyster mushrooms) are commercially cultivated in India owing to the favorable tropical agro-climatic conditions. However, there are only a few studies on the microbiome of mushrooms, especially oyster mushrooms. The aim of this study was to assess the effect of endobacteria on mycelial growth, spawning, sporophore development, and proximate composition of P. pulmonarius. We isolated several bacterial strains from the sporophores of P. pulmonarius and assessed the in vitro production of indole acetic acid, ammonia, and siderophores. The selected bacteria were individually supplemented with spawn, substrate, or both for sporophore production. Three of 130 isolates were selected as mycelial growth-promoting bacteria in both solid and submerged fermentation. These bacterial isolates were identified through Gram staining, biochemical characterization, and 16S rRNA sequencing. Isolate PP showed 99.24% similarity with Priestia paraflexa, whereas isolates PJ1 and PJ2 showed 99.78% and 99.65% similarities, respectively, with Rossellomorea marisflavi. The bacterial supplementation with spawn, substrate, or both, increased the biological efficiency (BE) and nutrient content of the mushrooms. The bacterial supplementation with substrate augmented BE by 64.84%, 13.73%, and 27.13% using PJ2, PP, and PJ1, respectively; under similar conditions of spawn supplementation, BE was increased by 15.24%, 47.30%, 48.10%, respectively. Overall, the supplementation of endobacteria to improve oyster mushroom cultivation may open a new avenue for sustainable agricultural practices in the mushroom industry.

Evaluation of Peripheral Versus Central Route of Ondansetron as Pretreatment to Prevent Pain on the Injection of Propofol: A Randomized Controlled Study.

Objective: We evaluated whether systemic ondansetron was also useful in the attenuation of propofol injection pain similar to ondansetron pretreatment. Methods: Eighty patients were enrolled. Patients in group S received ondansetron 4 mg in saline in the right hand followed 30 min later by 5 mL saline in the left hand along with venous occlusion. Group L patients received 4 mL of saline in the right hand followed by 5 mL 4 mg ondansetron in the left hand after 30 min. Two minutes later the occlusion was released. Patients received one-fourth of the calculated total dose of propofol, and their level of pain was graded on a scale of 0 to 3, with 0 denoting no discomfort. Mean blood pressure and heart rates were also recorded. Continuous variables were checked for normality using Shapiro-Wilks test. Normal continuous variables were expressed as mean standard deviation and non-normal continuous variables were expressed as median interquartile range. T-test for the difference in the mean and paired test were used for normally distributed continuous variable whereas Mann-Whitney U test-Wilcoxon test and sign test were used for non-normally distributed variables. Repeated measure analysis of variance was used for a variable measured over different periods of time to control for the baseline effect on subsequent measures. Results: Our results demonstrated that both systemic administration 30 min before and local venous pretreatment with ondansetron were equally beneficial in reducing pain during propofol injection. Conclusion: A systemic administration of ondansetron may play a role in the attenuation of propofol injection pain.

Correction: Gupta et al. Neutrophil Extracellular Traps Promote NLRP3 Inflammasome Activation and Glomerular Endothelial Dysfunction in Diabetic Kidney Disease. Nutrients 2022, 14, 2965.

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Comparison between in-plane and out-of-plane techniques for ultrasound guided cannulation of the left brachiocephalic vein in pediatric population: A randomised controlled trial.

BACKGROUND AND AIMS: Brachiocephalic vein is a novel site for central venous cannulation in infants. It becomes useful in patients where the internal jugular vein lumen is small (e.g., volume deficient patient), patients with a history of multiple cannulations, and in whom subclavian puncture is contraindicated. METHODS: In this randomized double-blinded study, 100 patients, aged between 0 and 1 year scheduled for elective central venous cannulation were recruited. The patients were allocated into two groups (50 patients in each). Group I patients had ultrasound (US) guided cannulation of the left brachiocephalic vein (BCV) by inserting a needle in-plane to the US probe from lateral to the medial direction, whereas Group II patients underwent cannulation of the BCV via an out-of-plane approach. RESULTS: The first-attempt success rate was significantly higher in Group I (74%) than in Group II (36%) (p < 0.001). The total success rate was higher in group I (98%) than in group II (88%) however the difference was statistically insignificant (p > 0.05). The mean BCV cannulation time was significantly shorter in group I (35.46 ± 25.10) than in group II (65.24 ± 40.26) (p < 0.001). The rate of unsuccessful BCV cannulation (12%) and hematoma development (12%) was significantly higher in group II than in group I (2%). CONCLUSION: Compared to the out-of-plane approach of left BCV cannulation, US-guided in-plane cannulation of the left BCV increased the first-attempt success rate, decreased the number of puncture attempts, and decreased the time required for cannulation.