Magnetically recoverable Fe3O4 nanocatalyst for the synthesis of biodynamically significant 1H-pyrazolo[1,2-b]phthalazine-5,10-diones derivatives and its DFT study.

An environmentally sustainable and proficient method is reported for the synthesis of medicinally important pyrazolo[1,2-b] phthalazine dione derivatives by aqueous micellar medium catalysed by Fe3O4 NPs. Dialkyl acetylenedicarboxylate with isocyanides in the presence of phthalhydrazide is used as starting material. The main advantages of this protocol are the availability of starting materials, short reaction times, green solvents and practical simplicity.

Transcriptional gene silencing in bread wheat (Triticum aestivum L.) and its application to regulate male fertility for hybrid seed production.

Transcriptional gene silencing (TGS) can offer a straightforward tool for functional analysis of plant genes, particularly in polyploid species such as wheat, where genetic redundancy poses a challenge in applying mutagenesis approaches, including CRISPR gene editing. In this study, we demonstrate efficient TGS in wheat, mediated by constitutive RNA expression of a promoter inverted repeat (pIR). pIR-mediated TGS of two anther-specific genes, TaMs45 and TaMs1, abolished their function resulting in male sterility. Whilst TGS of TaMs45 required transcriptional silencing of all three homoeologs, a B-genome-specific pIR for TaMs1 was sufficient to confer male sterility. We further show that the pIRs effect TGS of TaMs45 gene through DNA methylation of homologous promoter sequence, successfully suppressing transcription of all three homoeologs. Applying pIR-mediated TGS in wheat, we have generated a dominant male fertility system for production of hybrid seed and demonstrated the efficacy of this system under greenhouse and field conditions. This report describes the first successful TGS in wheat, whilst providing a dominant negative approach as alternative to gene knockout strategies for hybrid wheat breeding and seed production.

Efficient one-pot synthesis of substituted diphenyl 1, 3-thiazole through multicomponent reaction by using green and efficient Iron-catalyst via Cross-Dehydrogenative Coupling(CDC).

A clean and efficient, multi-component strategy for the synthesis of biologically important trisubstituted thiazole via the reaction of readily available barbituric acid, acetophenone, and aryl thioamides is reported in the presence of FeCl3.6H2O / O2(Air) in DMF solvent. The advantages of the present methodology include a one-pot reaction, environment-friendly approach, cost-effectiveness, broad substrate scope, operational simplicity, short reaction time, easy workup procedure, and high yields.

Male Fertility Genes in Bread Wheat (Triticum aestivum L.) and Their Utilization for Hybrid Seed Production.

Hybrid varieties can provide the boost needed to increase stagnant wheat yields through heterosis. The lack of an efficient hybridization system, which can lower the cost of goods of hybrid seed production, has been a major impediment to commercialization of hybrid wheat varieties. In this review, we discuss the progress made in characterization of nuclear genetic male sterility (NGMS) in wheat and its advantages over two widely referenced hybridization systems, i.e., chemical hybridizing agents (CHAs) and cytoplasmic male sterility (CMS). We have characterized four wheat genes, i.e., Ms1, Ms5, TaMs26 and TaMs45, that sporophytically contribute to male fertility and yield recessive male sterility when mutated. While Ms1 and Ms5 are Triticeae specific genes, analysis of TaMs26 and TaMs45 demonstrated conservation of function across plant species. The main features of each of these genes is discussed with respect to the functional contribution of three sub-genomes and requirements for complementation of their respective mutants. Three seed production systems based on three genes, MS1, TaMS26 and TaMS45, were developed and a proof of concept was demonstrated for each system. The Tams26 and ms1 mutants were maintained through a TDNA cassette in a Seed Production Technology-like system, whereas Tams45 male sterility was maintained through creation of a telosome addition line. These genes represent different options for hybridization systems utilizing NGMS in wheat, which can potentially be utilized for commercial-scale hybrid seed production.

Wheat ms5 male-sterility is induced by recessive homoeologous A and D genome non-specific lipid transfer proteins.

Nuclear male-sterile mutants with non-conditional, recessive and strictly monogenic inheritance are useful for both hybrid and conventional breeding systems, and have long been a research focus for many crops. In allohexaploid wheat, however, genic redundancy results in rarity of such mutants, with the ethyl methanesulfonate-induced mutant ms5 among the few reported to date. Here, we identify TaMs5 as a glycosylphosphatidylinositol-anchored lipid transfer protein required for normal pollen exine development, and by transgenic complementation demonstrate that TaMs5-A restores fertility to ms5. We show ms5 locates to a centromere-proximal interval and has a sterility inheritance pattern modulated by TaMs5-D but not TaMs5-B. We describe two allelic forms of TaMs5-D, one of which is non-functional and confers mono-factorial inheritance of sterility. The second form is functional but shows incomplete dominance. Consistent with reduced functionality, transcript abundance in developing anthers was found to be lower for TaMs5-D than TaMs5-A. At the 3B homoeolocus, we found only non-functional alleles among 178 diverse hexaploid and tetraploid wheats that include landraces and Triticum dicoccoides. Apparent ubiquity of non-functional TaMs5-B alleles suggests loss-of-function arose early in wheat evolution and, therefore, at most knockout of two homoeoloci is required for sterility. This work provides genetic information, resources and tools required for successful implementation of ms5 sterility in breeding systems for bread and durum wheats.

Concurrent modifications in the three homeologs of Ms45 gene with CRISPR-Cas9 lead to rapid generation of male sterile bread wheat (Triticum aestivum L.).

KEY MESSAGE: Hexaploid bread wheat is not readily amenable to traditional mutagenesis approaches. In this study, we show efficient utilization of CRISPR-Cas system and Next Generation Sequencing for mutant analysis in wheat. Identification and manipulation of male fertility genes in hexaploid bread wheat is important for understanding the molecular basis of pollen development and to obtain novel sources of nuclear genetic male sterility (NGMS). The maize Male sterile 45 (Ms45) gene encodes a strictosidine synthase-like enzyme and has been shown to be required for male fertility. To investigate the role of Ms45 gene in wheat, mutations in the A, B and D homeologs were produced using CRISPR-Cas9. A variety of mutations in the three homeologs were recovered, including a plant from two different genotypes each with mutations in all three homeologs. Genetic analysis of the mutations demonstrated that all three wheat Ms45 homeologs contribute to male fertility and that triple homozygous mutants are required to abort pollen development and achieve male sterility. Further, it was demonstrated that a wild-type copy of Ms45 gene from rice was able to restore fertility to these wheat mutant plants. Taken together, these observations provide insights into the conservation of MS45 function in a polyploid species. Ms45 based NGMS can be potentially utilized for a Seed Production Technology (SPT)-like hybrid seed production system in wheat.

Targeted mutagenesis of a conserved anther-expressed P450 gene confers male sterility in monocots.

Targeted mutagenesis using programmable DNA endonucleases has broad applications for studying gene function in planta and developing approaches to improve crop yields. Recently, a genetic method that eliminates the need to emasculate the female inbred during hybrid seed production, referred to as Seed Production Technology, has been described. The foundation of this genetic system relied on classical methods to identify genes critical to anther and pollen development. One of these genes is a P450 gene which is expressed in the tapetum of anthers. Homozygous recessive mutants in this gene render maize and rice plants male sterile. While this P450 in maize corresponds to the male fertility gene Ms26, male fertility mutants have not been isolated in other monocots such as sorghum and wheat. In this report, a custom designed homing endonuclease, Ems26+, was used to generate in planta mutations in the rice, sorghum and wheat orthologs of maize Ms26. Similar to maize, homozygous mutations in this P450 gene in rice and sorghum prevent pollen formation resulting in male sterile plants and fertility was restored in sorghum using a transformed copy of maize Ms26. In contrast, allohexaploid wheat plants that carry similar homozygous nuclear mutations in only one, but not all three, of their single genomes were male fertile. Targeted mutagenesis and subsequent characterization of male fertility genes in sorghum and wheat is an important step for capturing heterosis and improving crop yields through hybrid seed.

Pulmonary hypertension related to systemic sclerosis: points to consider for clinical trials.

There are proven successful approaches to clinical trial design in pulmonary arterial hypertension (PAH), which in turn have led to the licensing of a number of effective therapies. SSc has been included in trials of World Health Organization Group 1 PAH but has been under-represented. Responses in outcomes as diverse as exercise capacity, quality of life, durability of drug effect and survival have been reduced in comparison with those seen in idiopathic PAH. The PAH community has achieved international and interdisciplinary consensus guidelines for future studies. We consider the diverse outcome measures used in trials in the context of the complexities of scleroderma. An argument is advanced in favour of future trials focused exclusively on SSc but with adaptations of the core outcome measures and trial design templates applicable to more general studies of PAH.

Twenty-two points to consider for clinical trials in systemic sclerosis, based on EULAR standards.

OBJECTIVE: SSc is clinically and aetiopathogenically heterogeneous. Consensus standards for more uniform trial design and selection of outcome measures are needed. The objective of this study was to develop evidence-based points to consider (PTCs) for future clinical trials in SSc. METHODS: Thirteen international SSc experts experienced in SSc clinical trial design were invited to participate. One researcher with experience in systematic literature review and three trainees were also included. A systematic review using PubMed and the Cochrane Central Register of Controlled Trials was conducted and PTCs when designing clinical trials in SSc were developed. As part of that development we conducted an Internet-based Delphi exercise regarding the main points to be made in the consensus statement. Consensus was defined as achieving a median score of ≥7 of 9. RESULTS: By consensus, the experts decided to develop PTCs for each individual organ system. The current document provides a unifying outline on PTCs regarding general trial design, inclusion/exclusion criteria and analysis. Consensus was achieved regarding all the main points of the PTCs. CONCLUSION: Using European League Against Rheumatism suggestions for PTCs, a general outline for PTCs for controlled clinical trials in SSc was developed. Specific outlines for individual organ systems are to be published separately. This general outline should lead to more uniform and higher-quality trials and clearly delineate areas where further research is needed.

Production of viable gametes without meiosis in maize deficient for an ARGONAUTE protein.

Apomixis is a form of asexual reproduction through seeds in angiosperms. Apomictic plants bypass meiosis and fertilization, developing offspring that are genetically identical to their mother. In a genetic screen for maize (Zea mays) mutants mimicking aspects of apomixis, we identified a dominant mutation resulting in the formation of functional unreduced gametes. The mutant shows defects in chromatin condensation during meiosis and subsequent failure to segregate chromosomes. The mutated locus codes for AGO104, a member of the ARGONAUTE family of proteins. AGO104 accumulates specifically in somatic cells surrounding the female meiocyte, suggesting a mobile signal rather than cell-autonomous control. AGO104 is necessary for non-CG methylation of centromeric and knob-repeat DNA. Digital gene expression tag profiling experiments using high-throughput sequencing show that AGO104 influences the transcription of many targets in the ovaries, with a strong effect on centromeric repeats. AGO104 is related to Arabidopsis thaliana AGO9, but while AGO9 acts to repress germ cell fate in somatic tissues, AGO104 acts to repress somatic fate in germ cells. Our findings show that female germ cell development in maize is dependent upon conserved small RNA pathways acting non-cell-autonomously in the ovule. Interfering with this repression leads to apomixis-like phenotypes in maize.

To Study the Outcome of Cartilage Tympanoplasty Type I in Patients with Medium and Large Perforations Using 0.5 mm Sliced Conchal Cartilage Reinforced with Temporalis Fascia Grafts with 5 Years Follow-up.

Aims: To study the outcome of cartilage tympanoplasty type I in patients with medium and large perforations using 0.5 mm sliced conchal cartilage reinforced with temporalis fascia grafts with 5 years follow-up. Study Design: Retrospective clinical study. Patients and Method: 120 patients with dry tympanic membrane perforation medium and large size and intact ossicular chain, and with no history of previous ear surgery were selected. An underlay type one tympanoplasty, using 0.5 mm sliced conchal cartilage reinforced with temporalis fascia, was performed during 2018-19. A successful anatomical outcome was considered to comprise full, intact healing of the graft without perforation these patients were evaluated for at least 5 years post-operatively till 2023. Results: In this study graft uptake rate was 95.33% for medium size and 93.66% for large perforations at 3 months and after 5 years of follow-up 92.77% medium size and large size perforations were 89.67.66% (P < 0.001). Residual perforations were there in about 7.29% in medium and 10.33% in large size perfrations. Conclusion: Sliced conchal cartilage reinforced with temporalis fascia is a reliable technique for tympanoplasty, with improved graft uptake results in medium and large perforations in the long-term, also the residual perforations is significantly lower.

Synthesis of imidazole-fused nitrogen-bridgehead heterocycles catalysed by lipase and their antifungal and antimicrobial bioactivity.

An effective approach for selective C-N bond formation for synthesising imidazo[1,2-a] pyridine-based heterocycles using porcine pancreatic lipase (PPL) as a biocatalyst has been devised. Under moderate conditions, a series of imidazo[1,2-a]pyridine-based heterocycle derivatives were synthesised with remarkable selectivity in good-to-excellent yields (89-95%). Further, the antimicrobial and antifungal activities of derivatives 3ha, 3ka, 3fa, 3hc, and 3eb were observed, and they were found to be biologically active in antimicrobial susceptibility tests for Gram-positive bacteria (Enterococcus faecalis ATCC 29212 and Staphylococcus auris ATCC 25923), Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) and fungal strains (Candida albicans ATCC 90028 and Candida tropicalis ATCC 750).

Analysis of key factors influencing individual financial well-being using ISM and MICMAC approach.

A growing complexity in the financial world has attracted the interest of academicians and policymakers to examine the financial planning and well-being of individuals. This study attempts to explore the individual level determinants for improving financial well-being. Based upon the literature review, key enablers of individual financial well-being were identified which were then finalized by incorporating expert suggestions. Pursuant to this, six levels hierarchical structure was developed with the application of interpretive structural modeling (ISM) technique. Next, Matriced'ImpactsCroises Multiplication Appliques a un Classement (MICMAC) analysis was applied to determine the dependence and driving power of the identified variables. Our findings demonstrate that socio-economic factors and financial socialization are placed at the bottom level in the ISM hierarchy and all of them are also found to have the highest driving power under the MICMAC classification. On the other hand, healthy financial behaviors emerge on the top level and have the highest dependence power. The results of the study can provide valuable insights to financial educators and policymakers in terms of a better understanding of individual level enablers and their interrelationships. The knowledge of the importance of each enabler can enhance their capability to formulate improved strategies focused on securing the financial future of individuals. The concern of living a financially secured life is growing in a world full of economic uncertainties. Individual differences play a vital role in achieving a higher level of financial well-being. This study is one of the preliminary attempts to identify the individual level factors and rank them according to importance.

Atherosclerosis in systemic sclerosis: a systematic review and meta-analysis.

OBJECTIVE: Systemic sclerosis (SSc) is characterized by calcification, vasculopathy, and endothelial wall damage, all of which can increase the risk of developing atherosclerosis and cardiovascular disease. The aim of this study was to perform a systematic review and meta-analysis to determine whether the risk of atherosclerosis is increased in SSc patients compared to healthy individuals. METHODS: A systematic search was performed to identify studies published in PubMed and the Cochrane database up to May 2010, and recently published abstracts were also reviewed. Two reviewers independently screened articles to identify studies comparing the rate of atherosclerosis in SSc patients to that in healthy controls. The studies utilized one of the following methods: angiography, Doppler ultrasound to assess plaque and carotid intima-media thickness (IMT), computed tomography, magnetic resonance imaging, flow-mediated vasodilation (assessed as the FMD%), the ankle-brachial index, or autopsy. For carotid IMT and FMD% values, we computed a pooled estimate of the summary mean difference and explored predictors of carotid IMT using random-effects meta-regression. RESULTS: Of the 3,156 articles initially identified, 31 were selected for systematic review. The meta-analysis included 14 studies assessing carotid IMT and 7 assessing brachial artery FMD%. Compared to healthy controls, SSc patients had a higher prevalence of coronary atherosclerosis, peripheral vascular disease, and cerebrovascular calcification. Meta-analysis showed that SSc patients had increased carotid IMT (summary mean difference 0.11 mm, 95% confidence interval [95% CI] 0.05 mm, 0.17 mm; P = 0.0006) and lower FMD% (summary mean difference -3.07%, 95% CI -5.44%, -0.69%; P = 0.01) compared to controls. There was marked heterogeneity between the studies, which was mainly attributable to variations in disease duration and differences in the mean/median age between SSc patients and controls. CONCLUSION: Patients with SSc have an increased risk of atherosclerosis compared to healthy subjects. Further studies should elucidate the mechanism of this increased risk.

To Study the Long Term Outcome of Endoscopic Septoplasty with Microdebrider Assisted Inferior Turbinoplasty (MAIT) Versus Medial Flap Turbinoplasty (MFT).

To study the long term outcome of endoscopic septoplasty with microdebrider assisted inferior turbinoplasty (MAIT) versus medial flap turbinoplasty (MFT). The present study was conducted in the Department of ENT, Government Medical College, Amritsar. Patients with symptomatic persistent nasal obstruction were recruited from ENT outdoor clinics. The nasal obstruction was persistent despite medical therapy that included a minimum 4 weeks. The study was primarily a double blinded prospective randomized control study including 120 patients, where all patients enrolled at odd numbers were taken for endoscopic septoplasty with microdebrider assisted inferior turbinoplasty and all patients with even numbers were taken for endoscopic septoplasty with MFT. Patient-scored nasal obstruction (1-5) along with blindly assessed nasal airway patency ratings (1-4) was done at 3 and 24 months postoperatively. A total of 120 patients were recruited in the study. The mean ages of the MAIT and MFT groups were 28.61 ± 14.8 and 30.25 ± 8.36 years, respectively. Average follow-up period was 21.9 ± 6.3 months. Nasal obstruction was improved in both techniques at 3 months, but after long term follow up, it was highly significant for MFT along with improvement in preoperative symptoms p < 0.001. No patients complained of worsening of their obstruction. Nasal patency at 24 months, a significant proportion of patients had a greater nasal assessment by a blind assessor with 97.1% in MFT and 81.9% MAIT with mild to no obstruction. In MAIT group 16.6% had pain/discomfort, 23.6% had discharge which were the major complications, but crusting (MAIT 10% and MFT 3.3%), adhesions (MAIT 13.8% and MFT 1.6%). The medial flap inferior turbinoplasty (MFT) is technically straight forward procedure that provides long term more effective and satisfactory the patient in relieving nasal obstruction, without significant risk of complications. The long term follow up of MAIT is required as there was increase in need of decongestion and they might require second procedure as MFT.

An Unusual Case of a Pediatric Nasal Septal Abscess with Life-Threatening Complications in COVID-19 Pandemic.

In this modern era, when access to healthcare services is improved, and awareness among the general population is enhanced, the presentation of mere septal abscess of the nose as a fatal complication is less common. Due to various lockdown restrictions in the COVID-19 scenario and fear to contract an infection, patients are presenting late to the health care setting for proper management. We treated an 11-year old child of complicated nasal septal abscess who responded well to aspiration of pus and medical treatment. Our patient is a rare case report who progressed from vestibulitis to septal abscess and further leading to sinusitis, orbital, and intracranial complications.

Comparative Study of the Management of Intertrochanteric Fracture Femur With Proximal Femoral Nail vs. the Dynamic Hipscrew With Derotation Screw in Elderly Population.

BACKGROUND: Intertrochanteric fractures can be treated, both by conservative and operative methods depending upon the status of the patient. The purpose of this study was to assess the functional outcome of intertrochanteric fracture of femur treated with dynamic hip screw (DHS) with de-rotation screw comparing and proximal femoral nail (PFN). METHODOLOGY: We compared 30 (male: 23, female: seven) cases of intertrochanteric fractures with a mean age of the population was 65 years and male to female ratio in was 2.75:1. Patients were recruited in this study having inclusion criteria of adults above 50 years of age, isolated intertrochanteric fractures of the AO Foundation/Orthopaedic Trauma Association (AO/OTA) type A1 and A2, fracture less than two weeks, and intertrochanteric fracture with or without distal extension. RESULTS: Post-operatively, patients treated by either of these two methods were statistically analyzed in terms of comparing advantages and disadvantages in terms of the time of fracture union and outcome of both above-mentioned procedures using Harris hip score. CONCLUSION: PFN gives better results than DHS with De-Rotation Screw-in intertrochanteric fractures in terms of the amount of blood loss during surgery, duration of surgery, early toe-touch weight-bearing, and Harris hip scores. There is no difference between the two modalities in terms of duration of hospitalization, fracture union, mortality and morbidity, and postoperative complications.

Thyroid function in patients with idiopathic nephrotic syndrome.

BACKGROUND: Albumin is the major protein excreted in urine in patients with nephrotic syndrome (NS). However, low-molecular-weight proteins including some binding proteins are also excreted. Thyroid hormone and its binding globulins are excreted in urine in excess in nephrotic syndrome. Therefore, it has been postulated that patients with nephrotic syndrome may show hypothyroidism, subclinical or overt. METHODS: In this prospective observational study, patients of idiopathic nephrotic syndrome aged 1-40 years of both gender were included. Serum T3, T4 and TSH were assayed at diagnosis and repeated at 12 weeks or at remission whichever was earlier. Renal biopsy was performed as required. RESULTS: Among 100 patients taken for analysis (42 children, 58 adult), 30 cases were of first episode, 40 were of frequent relapse/steroid-dependent NS, and 30 patients had steroid-resistant NS (SRNS). Three (3%) cases had overt hypothyroidism and 18 (18%) patients had subclinical hypothyroidism. Most hypothyroid cases belonged to SRNS subgroup. Mean Serum T3, T4 and TSH values showed significant improvement in remission in comparison to nephrosis state (P < 0.01). Serum TSH had significant positive correlation (r = 0.391, P < 0.01) with 24-h proteinuria and negative correlation with serum albumin (r = - 0.303, P < 0.01) in nephrosis. CONCLUSION: Hypothyroidism is common among nephrotic syndrome patients especially in SRNS subgroup. Therefore, routine screening is recommended in steroid-resistant nephrotic syndrome patients.

Mobile application to optimize care for ST-segment elevation myocardial infarction patients in a large healthcare system, STEMIcathAID: rationale and design.

Aims: Technological advancements have transformed healthcare. System delays in transferring patients with ST-segment elevation myocardial infarction (STEMI) to a primary percutaneous coronary intervention (PCI) centre are associated with worse clinical outcomes. Our aim was to design and develop a secure mobile application, STEMIcathAID, streamlining communication, and coordination between the STEMI care teams to reduce ischaemia time and improve patient outcomes. Methods and results: The app was designed for transfer of patients with STEMI to a cardiac catheterization laboratory (CCL) from an emergency department (ED) of either a PCI capable or a non-PCI capable hospital. When a suspected STEMI arrives to a non-PCI hospital ED, the ED physician uploads the electrocardiogram and relevant patient information. An instant notification is simultaneously sent to the on-call CCL attending and transfer centre. The attending reviews the information, makes a video call and decides to either accept or reject the transfer. If accepted, on-call CCL team members receive an immediate push notification and begin communicating with the ED team via a HIPAA compliant chat. The app provides live GPS tracking of the ambulance and frequent clinical status updates of the patient. In addition, it allows for screening of STEMI patients in cardiogenic shock. Prior to discharge, important data elements have to be entered to close the case. Conclusion: We developed a novel mobile app to optimize care for STEMI patients and facilitate electronic extraction of relevant performance metrics to improve allocation of resources and reduction of costs.

The differential expression of aqueous soluble proteins in breast normal and cancerous tissues in relation to stage and grade of patients.

Breast cancer is a leading cause of female deaths worldwide. In Malaysia, it is the most common form of female cancer while Infiltrating ductal carcinoma (IDC) is the most common form of breast cancer. A proteomic approach was used to identify changes in the protein profile of breast cancerous and normal tissues. The patients were divided into different cohorts according to tumour stage and grade. We identified twenty-four differentially expressed hydrophilic proteins. A few proteins were found significantly related to various stages and grades of IDC, amongst which were SEC13-like 1 (isoform b), calreticulin, 14-3-3 protein zeta, and 14-3-3 protein eta. In this study, we found that by defining the expression of the proteins according to stages and grades of IDC, a significant relationship between the expression of the proteins with the stage or grade of IDC can be established, which increases the usefulness of these proteins as biomarkers for IDC.