Iatrogenically Acquired Mycobacterium abscessus Infection in an Indwelling Intercostal Drainage In Situ in a Patient With Alcoholic Liver Disease and Bilateral Hepatic Hydrothorax: A Report of a Rare Case.

A 47-year-old male, a known case of alcoholic chronic liver disease with portal hypertension, presented with complaints of abdominal distension and shortness of breath. A provisional diagnosis of ethanol-related compensated chronic liver disease (CLD) with portal hypertension and splenomegaly, gross ascites with bilateral hepatic hydrothorax was made. The left-sided pleural effusion subsided after three pleural taps, but the right-sided effusion kept refilling even after four to five days of repeated therapeutic taps, so a pigtail catheter was left in situ. The pleural fluid was sent for culture which did not grow any pathogenic organisms. Cartridge-based nucleic acid amplification tests where Mycobacterium tuberculosis complex (MTBC) was not detected, Ziehl-Neelsen staining was done in which acid-fast bacilli were not seen, and cytology was done where no malignant cells were seen. The patient was discharged with the pigtail in situ on the right side and, after 20 days, the patient again presented with shortness of breath, and imaging revealed moderate right-side pleural effusion. Draining of pleural fluid was done and sent for investigation which again revealed no infective etiology. The patient was admitted to the hospital for one month as the right-sided effusion did not resolve. Suddenly, the patient developed shortness of breath, and a chest X-ray was done, which showed pigtail blockage; pigtail flushing was done, and the bag was drained. The patient was empirically started on IV meropenem 500 mg TID, IV teicoplanin 400 mg BD, and inj polymyxin B 500,000 IU IV BD. The pleural fluid was sent continuously for investigation for the first two months which again did not reveal any infective etiology. After two months of pigtail in situ, the pleural fluid was sent for CBNAAT where MTBC was not detected, and ZN stain showed smooth acid-fast bacilli. The sample was cultured, and it grew acid-fast bacilli in 72 hours on blood agar, MacConkey agar, and Lowenstein-Jensen media. A line probe assay done from the isolate revealed it to be Mycobacterium abscessus subsp. abscessus which was resistant to macrolides and sensitive to aminoglycosides. Mycobacterium abscessus subsp. abscessus was isolated from repeated cultures of pleural fluid, and the patient was advised on a combination treatment of amikacin, tigecycline, and imipenem. The patient was discharged with the indwelling pigtail with the advised treatment; unfortunately, we lost patient follow-up as the patient never returned to us.

Sodium-Glucose Cotransporter 2 Inhibitor-Induced Euglycemic Diabetic Ketoacidosis: The Other Side of the Coin!

Euglycemic diabetic ketoacidosis (EDKA) though rare is a life-threatening complication of sodium-glucose cotransporter 2 (SGLT2) inhibitors. With their increasing use in the management of type 2 diabetes mellitus (T2DM) due to long-term beneficial effects, the incidence of this complication is on the rise. We report a case of a 58-year-old lady with a history of T2DM on multiple anti-diabetes medications including dapagliflozin for one year, who during intercurrent illness developed EDKA. Her blood sugar on admission was 203 mg/dL, and arterial blood gas showed high anion-gap metabolic acidosis (HAGMA) with ketonuria and ketonemia (blood beta-hydroxybutyric (BOHB) acid level: 5.4 mmol/L). Low carbohydrate intake, dehydration resulting from repeated vomiting, and skipping the previous two days' dose of insulin could have precipitated this condition. She was treated with intravenous fluids, insulin, 5% dextrose infusion, and potassium supplements with complete resolution of acidosis after about 90 hours. This case signifies the importance of awareness of the link between the use of SGLT2 inhibitors and EDKA and early recognition of this complication to reduce morbidity and mortality. Furthermore, it also emphasizes the need for clinicians to educate their patients taking these drugs to stop them during the intercurrent illness to prevent them from developing EDKA.

Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow-up.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post-tubercular lung disease. However, some evidence suggests that CPA might co-exist in patients with newly-diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end-of-TB-therapy. MATERIALS AND METHODS: This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end-of-TB-therapy with symptom assessment, anti-Aspergillus IgG antibody and imaging of chest for diagnosing CPA. RESULTS: We recruited 255 patients at baseline out of which 158 (62%) completed their follow-up. Anti-Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end-of-TB-therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end-of-TB-therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end-of-TB-therapy. CONCLUSIONS: CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti-tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies.

Pd(II) complexes bearing NNS pincer ligands: unveiling potent cytotoxicity against breast and pancreatic cancer.

The continuously increasing rate of breast cancer is one of the major threats to female health worldwide. Recently, palladium complexes have emerged as impressive candidates with effective biocompatibility and anticancer activities. Hence, in the present study, we report a new series of palladium complexes bearing NNS pincer ligands for cytotoxicity studies. The reaction of thiophenol/4-chlorothiophenol/4-methylthiophenol/4-methoxythiophenol with 2-bromo-N-quinolin-8-yl-acetamide in the presence of sodium hydroxide in ethanol at 80 °C gave [C9H6N-NH-C(O)-CH2-S-Ar] [Ar = C6H5 (L1), C6H4Cl-4 (L2), C6H4Me-4 (L3), and C6H4-OMe-4 (L4)]. The corresponding reaction of L1-L4 with Na2PdCl4 in methanol at room temperature for 3 h resulted in complexes [(L1-H)PdCl] (C1), [(L2-H)PdCl] (C2), [(L3-H)PdCl] (C3), and [(L4-H)PdCl] (C4). All new compounds have been characterized by spectroscopic analyses. The structures of complexes C1, C3, and C4 have also been determined from single-crystal X-ray diffraction data. The cytotoxicities of L1-L4 and C1-C4 have been investigated for breast cancer 4T1 and pancreatic cancer MIA-PaCa-2 cells. The IC50 values for complexes C2 and C3 were observed to be comparable to or higher than those of cisplatin. The stressed morphology and cell death of cancerous cells were successfully observed through cellular morphology analysis and the assessment of cytoskeleton damage.

TEX13B is essential for metabolic reprogramming during germ cell differentiation.

STUDY QUESTION: What is the functional significance of Tex13b in male germ cell development and differentiation? SUMMARY ANSWER: Tex13b regulates male germ cell differentiation by metabolic reprogramming during spermatogenesis. WHAT IS KNOWN ALREADY: Studies in mice and humans suggest that TEX13B is a transcription factor and is exclusively expressed in germ cells. STUDY DESIGN, SIZE, DURATION: We sequenced the coding regions of TEX13B in 628 infertile men and 427 ethnically matched fertile control men. Further, to identify the molecular function of Tex13b, we created a Tex13b knockout and conditional overexpression system in GC-1spg (hereafter, GC-1) cells. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our recent exome sequencing study identified novel candidate genes for male infertility. TEX13B was found to be one of the potential candidates, hence we explored the role of TEX13B in male infertility within a large infertile case-control cohort. We performed functional analyses of Tex13b in a GC-1 cell line using CRISPR-Cas9. We differentially labelled the cell proteins by stable isotope labelling of amino acids in cell culture (SILAC) and performed mass spectrometry-based whole-cell proteomics to identify the differential protein regulation in knockout cells compared to wild-type cells. We found that Tex13b knockout leads to downregulation of the OXPHOS complexes and upregulation of glycolysis genes, which was further validated by western blotting. These results were further confirmed by respirometry analysis in Tex13b knockout cells. Further, we also performed a conditional overexpression of TEX13B in GC-1 cells and studied the expression of OXPHOS complex proteins by western blotting. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a rare variant, rs775429506 (p.Gly237Glu), exclusively in two non-obstructive-azoospermia (NOA) men, that may genetically predispose these men for infertility. Further, we demonstrated that Tex13b functions in the transcription regulation of OXPHOS complexes. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: We examined the function of Tex13b in GC-1 in vitro by knocking out and conditional overexpression, for understanding the function of Tex13b in germ cells. Unfortunately, this could not be replicated in either an animal model or in patient-derived tissue due to the non-availability of an animal model or patient's testis biopsies. WIDER IMPLICATIONS OF THE FINDINGS: This study identified that Tex13b plays an important role in male germ cell development and differentiation. The findings of this study would be useful for screening infertile males with spermatogenic failure and counselling them before the implementation of assisted reproduction technique(s). STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the Council of Scientific and Industrial Research (CSIR) under the network project (BSC0101 and MLP0113) and SERB, the Department of Science and Technology, Government of India (J C Bose Fellowship: JCB/2019/000027). The authors do not have any competing interest.

In vitro and in silico investigation of glycyrrhizic acid encapsulated zein nanoparticles: A synergistic targeted drug delivery approach for breast cancer.

This study presents an innovative approach for targeted drug delivery through the development of Glycyrrhizic acid-loaded zein nanoparticles (GA-LNPs) as a proficient carrier system. The juxtaposition of zein, a hydrophobic biological macromolecule as a protein carrier, and Glycyrrhizic acid (GA), a hydrophilic therapeutic compound, exemplifies the adaptability of hydrocolloids within cutting-edge drug delivery systems. The characterization and functional traits of research encompass multifaceted analyses of natural macromolecules, which elucidate the homogeneous and spherical morphology of GA-LNPs with an average size of 170.49 nm. The controlled drug release profile of GA, orchestrated under simulated gastrointestinal conditions, adheres to diffusion-based Higuchi kinetics, reflecting the controlled release of the natural macromolecules. The intermolecular interactions among Zein, GA, and cross-linker EDC, facilitated through molecular dynamics simulations, fortify the structural integrity of the encapsulation matrix. In Vitro studies revealed enhanced cellular uptake of GA-LNPs in MCF-7 breast cancer cells. This cellular internalization was further confirmed through cytotoxicity assessments using MTT and apoptosis assays (fluorescence microscopy), which demonstrated the prominent anticancer effects of GA-LNPs on MCF-7 in time/dose-dependent manner. The successful formulation of GA-LNPs, coupled with their sustained release and potent anticancer properties, makes them a potential platform for advanced targeted therapeutic strategies in biomedical applications.

Truncated variants of thyroid hormone receptor beta display disease-inflicting malfunctioning at cellular level.

Thyroid hormone receptor ß (THRß) is a member of the nuclear receptor superfamily of ligand-modulated transcription factors. Upon ligand binding, THRß sequentially recruits the components of transcriptional machinery to modulate target gene expression. In addition to regulating diverse physiological processes, THRß plays a crucial role in hypothalamus-pituitary-thyroid axis feedback regulation. Anomalies in THRß gene/protein structure are associated with onset of diverse disease states. In this study, we investigated disease-inflicting truncated variants of THRß using in-silico analysis and cell-based assays. We examined the THRß truncated variants on multiple test parameters, including subcellular localization, ligand-receptor interactions, transcriptional functions, interaction with heterodimeric partner RXR, and receptor-chromatin interactions. Moreover, molecular dynamic simulation approaches predicted that shortened THRß-LBD due to point mutations contributes proportionally to the loss of structural integrity and receptor stability. Deviant subcellular localization and compromised transcriptional function were apparent with these truncated variants. Present study shows that 'mitotic bookmarking' property of some THRß variants is also affected. The study highlights that structural and conformational attributes of THRß are necessary for normal receptor functioning, and any deviations may contribute to the underlying cause of the inflicted diseases. We anticipate that insights derived herein may contribute to improved mechanistic understanding to assess disease predisposition.

Synthesis, physiochemical characterization, molecular docking study, and anti-breast cancer activity of silymarin loaded zein nanoparticles.

Breast cancer is a major cause of death in women worldwide leading to requirement of new therapeutic strategies. Silymarin demonstrated the anti-cancer activity however, due to low bioavailability its use is restricted. This study aimed to improve the solubility of silymarin by developing a silymarin loaded zein nanoparticles (SLNPs) which was stabilized by beta cyclodextrin. Comprehensive physiochemical characterization studies based on DLS, FTIR, UV-Vis Spectroscopy, FE-SEM, TEM, XRD, DSC, NMR and TGA confirmed the successful synthesis of SLNPs via an anti-solvent precipitation method. FE-SEM and TEM images demonstrated the uniform size and spherical shape of nanoparticles with encapsulation and loading efficiencies of 84.32 ± 1.9 % and 15.25 ± 2.4 % respectively. The zein protein interaction with silymarin, and ß-cyclodextrin was shown to be beneficial via the use of molecular simulations and binding energy calculations. Cellular studies demonstrated dose and time dependent cytotoxicity of SLNPs on MCF-7 breast cancer cell. FACS, qRT-PCR and Western blotting showed Bax (pro-apoptotic) upregulation while Bcl-2 (anti-apoptotic) downregulation. Our findings suggest that these loaded nanoparticles are more efficient than pure drug, enhancing its bioavailability and paving the path for developing it as a promising nutraceutical to treat breast cancer.

Phytoformulation with hydroxycitric acid and capsaicin protects against high-fat-diet-induced obesity cardiomyopathy by reducing cardiac lipid deposition and ameliorating inflammation and apoptosis in the heart.

Background and aim: Phytoformulation therapy is a pioneering strategy for the treatment of metabolic disorders and related diseases. The aim of the present study was to investigate the protective effect of a phytoformulation consisting of hydroxycitric acid and capsaicin against obesity-related cardiomyopathy. Experimental procedure: Sprague-Dawley rats were fed HFD for 21 weeks, and phytoformulation (100 mg/kg body weight) was administered orally for 45 days starting at week 16. Results and conclusion: We found that HFD supplementation resulted in significant hyperglycemia and caused an increase in cardiac lipid deposition, inflammation and apoptosis in the heart. Phytoformulation therapy not only significantly decreased blood levels of glucose, cholesterol, triglycerides, free fatty acids, and inflammatory cytokines in obese rats, but also protected cardiac tissue, as shown by histological analysis. Conversely, phytoformulation therapy decreased mRNA levels for sterol regulatory element-binding factor 1, fatty acid synthase, acetyl-CoA carboxylase, and fatty acid binding protein 1 genes involved in fatty acid synthesis and absorption in obese rats. It increased the levels of lysosomal acid lipase, hormone-sensitive lipase, and lipoprotein lipase genes involved in fatty acid degradation in the heart. In addition, the phytoformulation improved cardiac inflammation and apoptosis by downregulating the genes nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB), tumour necrosis factor α, interleukin-6, toll-like receptor-4 (TLR-4), BCL2-associated X and caspase-3. In conclusion, our results show that the phytoformulation improved insulin sensitivity and attenuated myocardial lipid accumulation, inflammation, and apoptosis in the heart of HFD-induced obese rats by regulating fatty acid metabolism genes and downregulating NF-kB/TLR-4/caspase-3.

Soil-mustard revitalization via rice husk ash, a promising soil amendment material for sustainable management of heavy metal contamination in tropical ecosystem.

Prolonged wastewater irrigation in agriculture has led to the accumulation of heavy metals in soil, endangering both the soil quality and food safety, thereby posing a potential threat to human health through the consumption of contaminated crops. The present study aimed to enhance the yield of mustard (Brassica juncea L. cv. Varuna and NRCHB 101) plants and stabilize heavy metals (Cd, Cr, Ni, Cu, and Zn) in wastewater-irrigated soil using rice husk ash (RHA), rice mill by-product, collected from Chandauli region of Eastern Uttar Pradesh, India. Results demonstrated significant improvements in growth, biomass, physiology, and yield of mustard plant with increasing RHA application in wastewater irrigated soil (p ≤ 0.05). Heavy metal accumulation in different parts of mustard plants decreased as RHA application rate increased. Applying RHA at 2% in soil proved to be most effective in reducing Cd, Cr, Ni, Cu, and Zn accumulation in seeds by 29%, 29.6%, 23.1%, 21.3% and 20.1%, respectively in Varuna and 30.1%, 21.4%, 11.1%, 12.1%, and 28.5%, respectively in NRCHB 101cultivars. The present findings showed that RHA amendment in wastewater irrigated soil had reduced bioaccumulation of Cd, Cr, Ni, Cu, and Zn and consequently their toxicity in cultivated mustard plants. A novel application of RHA is unveiled in this research, offering a promising solution to promote sustainable agriculture and to reduce heavy metal associated health risks within the soil-mustard system.

Buccal versus buccal palatal infiltration for pulpal anesthesia using 2% lidocaine and 4% articaine: A randomized controlled trial.

Background: The inability in achieving complete pulpal anesthesia with standard buccal infiltration especially in cases with SIP used for maxillary teeth. The study aimed to compare the anesthetic efficacy of buccal and buccal plus palatal infiltration technique using 2% lidocaine and 4% articaine in permanent maxillary first molars with the diagnosis of symptomatic irreversible pulpitis (SIP). Material and method: One hundred and twenty-three patients with clinical diagnosis of SIP, aged 18-50 years were randomly allocated to three treatment groups (N = 41). Group 1(BIL): Buccal infiltration technique using 2% lidocaine with 1:80,000 adrenaline. Group 2(BPIL): combination of buccal plus palatal infiltration using 2% Lidocaine with 1:80,000 adrenaline. Group 3(BIA): Buccal infiltration using 4% articaine with 1:100,000 adrenaline. Pain intensity of patients were recorded before and after the administration of local anesthesia during endodontic procedure that is during caries removal, access preparation and pulp removal using Heft-Parker Visual Analog Scale (HP-VAS). Success was defined by "no pain (0 mm)" or "mild pain (0-54 mm)" during endodontic procedure. The anesthetic efficacy rates were analyzed using chi-square tests, age differences using one-way ANOVA. Results: The final analysis included total of 117 patients. Higher success was observed in group II (85%) in comparison to group I (69%) and group III (74%), but the difference was statistically nonsignificant (p > 0.05). Our results demonstrated a nonsignificant difference between genders in all three groups (p > 0.05). Conclusion: The use of buccal plus palatal infiltration and 4% articaine can provide effective anesthesia as standard buccal infiltration and 2% lidocaine for patients with SIP in maxillary first molars.

Folate conjugated albumin as a targeted nanocarrier for the delivery of fisetin: in silico and in vitro biological studies.

Fisetin (FST), a natural flavonoid compound derived from various fruits and vegetables, including apple, strawberry, and onion, demonstrates potential for a wide range of pharmaceutical applications, including potential anticancer properties. However, challenges such as low bioavailability, poor aqueous solubility, and limited permeability restrict the use of FST in the pharmaceutical sector. Nowadays, targeted nanomedicines have garnered attention to overcome limitations associated with phytochemicals, including FST. In the present study, we have designed and successfully prepared folate-targeted FST nanoparticles (FFNPs). Characterization through DLS and FE-SEM revealed the successful preparation of monodisperse (PDI: 0.117), nanoscale-sized (150 nm), and spherical nanoparticles. Physicochemical characterization including FTIR, XRD, DSC, and TGA analysis, confirmed the encapsulation of the FST within the Folic acid (FA) - conjugated nanoparticles (CNPs) and revealed its amorphous nature. Molecular docking analysis revealed the strong binding affinity and specific amino acid interactions involved in the BSA-FST-FA complex, suggesting the potential synergistic effect of FST and FA in enhancing the therapeutic activity of the FFANPs. Cytotoxic assessments by the MTT assay, migration assay, AO-EtBr staining assay, colony formation assay, and cellular uptake study demonstrated enhanced anticancer efficacy, apoptosis induction, and enhanced uptake of FFNPs compared to pure FST. These findings propose prepared FFNPs as a promising targeted drug delivery nanocarrier for effective FST delivery in cancer therapy.

Screening of mustard cultivars for phytoremediation of heavy metals contamination in wastewater irrigated soil systems.

The mustard (Brassica juncea L.) plant is a well-known and widely accepted hyper-accumulator of heavy metals. The genetic makeup of mustard's cultivars may significantly impact their phytoremediation capabilities. The present study aimed to investigate the growth performance, yield attributes, and heavy metal accumulation potential of B. juncea cv. Varuna, NRCHB 101, RH 749, Giriraj, and Kranti, cultivated in soil irrigated with wastewater (EPS) and bore-well water (MPS). EPS contributed more Cr, Cd, Cu, Zn, and Ni to tested mustard cultivars than the MPS. EPS reduced morphological, biochemical, physiological, and yield attributes of tested mustard cultivars significantly (p < 0.05) than the MPS. Among the tested cultivars of mustard plants, Varuna had the highest heavy metal load with the lowest harvest index (35.8 and 0.21, respectively). Whereas NRCHB 101 showed the lowest heavy metal load with the highest harvest index (26.9 and 0.43, respectively). The present study suggests that B. juncea cv. Varuna and NRCHB 101 could be used for the phytoextraction of heavy metals and reducing their contamination in food chain, respectively in wastewater irrigated areas of peri-urban India. The outcomes of the present study can also be utilized to develop a management strategy for sustainable agriculture in heavy metal polluted areas resulting from long-term wastewater irrigation.

Cr- and Ga-Modified ZSM-5 Catalyst for the Production of Renewable BTX from Bioethanol.

Light aromatics (benzene, toluene, and xylene, collectively known as BTX) are essential commodity chemicals in the petrochemical industry. The present study examines the aromatization of bioethanol with Cr- and Ga-modified ZSM-5. Both Cr and Ga were incorporated by the ion-exchange method. Cr-modified ZSM-5 outperforms the Ga-modified ZSM-5 and H-ZSM-5 catalysts. Cr-H-ZSM-5 almost doubled the carbon yield of aromatics compared to H-ZSM-5 at an optimum reaction temperature of 450 °C. Cr-H-ZSM-5 produced aromatics with a yield of ~40 %. The effect of dilution in feed on BTX production is also studied. Cr-H-ZSM-5 was found to be more active than H-ZSM-5. Complete ethanol conversion was obtained with both pure and dilute bioethanol. The Bronsted-Lewis acid (BLA) pair formed after metal incorporation is responsible for dehydrogenation followed by aromatization, leading to increased aromatic production.

First Case of Nocardia wallacei From India: A Case Report and Literature Review.

Nocardia is a type of bacteria that can cause infections in both immunocompromised and immunocompetent hosts. It is an obligate aerobe and is commonly found in the environment. Pulmonary nocardiosis may present as pneumonia, endobronchial inflammatory masses, lung abscess, and cavitary disease with contiguous extension, leading to effusion and empyema. We present a case of pulmonary nocardiosis in a 75-year-old male patient with type 2 diabetes mellitus. The patient presented with bilateral pneumonia and hypoxia with an oxygen saturation of 85%. Sputum samples were sent to the microbiology laboratory for testing. Acid-fast staining with 1% H2SO4 showed acid-fast branching filamentous rods, but Nocardia could not be isolated in culture. The sample was subjected to 16S rRNA gene sequencing, which identified the pathogen as Nocardia wallacei. The culture of the sputum did not grow any pathogenic organisms, and the blood culture was sterile. Unfortunately, the patient left the hospital against medical advice as he was advised for intubation. The patient could not survive and died the next day after leaving the hospital. N. wallacei can be fatal and cause disseminated infection in both immunosuppressed and immunocompetent patients. Only eight case reports of N. wallacei have been reported in the literature from various parts of the world. Our case is the first case report of N. wallacei from India.

Effect of Intraligamentary Tramadol Hydrochloride on Anesthetic Success During Endodontic Management of Mandibular Molars: A Randomized Clinical Controlled Trial.

OBJECTIVE: Tramadol hydrochloride has shown local anesthetic properties similar to lidocaine, apart from a central analgesic effect. The present study evaluated the effect of the administration of tramadol alone or in addition to 2% lidocaine, as supplementary intraligamentary injections. METHODS: One hundred and five patients, with a failed primary inferior alveolar nerve block (IANB), were randomly allocated to one of the three supplementary intraligamentary groups: 2% lidocaine with 1: 80,000 epinephrine; tramadol hydrochloride (50 mg/mL); and 2% lidocaine with 1: 80,000 epinephrine plus tramadol hydrochloride. Patients received 1.2 mL doses (0.6 mL of each root). Patients reporting pain ≤54 on Heft Parker visual analogue scale (Heft-Parker VAS), were categorized as successful anesthesia. A finger pulse oximeter was used to measure the heart rates. The anesthetic success rates, gender, and type of tooth were compared using the Pearson chi-square test. The heart rates and age were statistically evaluated using the one-way analysis of variance test. The level of significance was set at 0.05 (p=0.05). RESULTS: The initial IANB was successful in 31% of cases. There were significant differences in the anesthetic success rates of different supplementary intraligamentary injections (χ2= 33.6, p<0.001, df=2). The 2% lidocaine-plus-tramadol resulted in significantly higher success rates than the two groups. There were no significant changes in the baseline heart rates of all groups (p>0.05). CONCLUSION: The addition of tramadol to 2% lidocaine with 1: 80,000 epinephrine, given as supplementary intraligamentary injection, can help in achieving successful anesthesia during the endodontic management of mandibular molars with irreversible pulpitis resistant to IANB injections.

Insights into the management of food waste in developing countries: with special reference to India.

Up to one third of the food that is purposely grown for human sustenance is wasted and never consumed, with adverse consequences for the environment and socio-economic aspects. In India, managing food waste is a significant environmental concern. Food waste output is increasing in Indian cities and towns as a result of the country's urban expansion, modernization, and population growth. Poor management of food waste can have negative consequences for the environment and pose a risk to the public's health issues. This review focuses on the current challenges, management strategies, and future perspectives of food waste management in India. The efficient management of food waste involves a comprehensive study regarding the characterization of food waste and improved waste management methods. In addition, the government policies and rules for managing food waste that is in effect in India are covered in this review.

Immunogenicity of cancer cells: An overview.

The immune system assumes a pivotal role in the organism's capacity to discern and obliterate malignant cells. The immunogenicity of a cancer cell pertains to its proficiency in inciting an immunological response. The prowess of immunogenicity stands as a pivotal determinant in the triumph of formulating immunotherapeutic methodologies. Immunotherapeutic strategies include immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and on vaccines. Immunogenic cell death (ICD) epitomizes a form of cellular demise that incites an immune response against dying cells. ICD is characterized by the liberation of distinct specific molecules that activate the immune system, thereby leading to the identification and elimination of dying cells by immunocytes. One of the salient characteristics inherent to the ICD phenomenon resides in the vigorous liberation of adenosine triphosphate (ATP) by cellular entities dedicated to embarking upon the process of programmed cell death, yet refraining from complete apoptotic demise. ICD is initiated by a sequence of molecular events that occur during cell death. These occurrences encompass the unveiling or discharge of molecules such as calreticulin, high-mobility group box 1 (HMGB1), and adenosine triphosphate (ATP) from dying cells. These molecules act as "eat me" signals, which are recognized by immune cells, thereby prompting the engulfment and deterioration of expiring cells by phagocytes including various pathways such as Necroptosis, Apoptosis, and pyroptosis. Here, we review our current understanding of the pathophysiological importance of the immune responses against dying cells and the mechanisms underlying their activation. Overall, the ICD represents an important mechanism by which the immune system recognizes and eliminates dying cells, including cancer cells. Understanding the molecular events that underlie ICD bears the potential to engender innovative cancer therapeutics that harness the power of the immune system to combat cancer.

The Efficacy of Angiotensin Receptor-Neprilysin Inhibitor Versus Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Post Myocardial Infarction: A Meta-Analysis.

Acute myocardial infarction (MI) is one of the leading global healthcare emergencies, contributing to over three million global deaths. The purpose of this study is to investigate further the efficacy of sacubitril/valsartan over angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in reducing the risk of heart failure (HF) in post-MI patients and providing a clear evidence-based medicine guideline for future use. An electronic database search was conducted on English databases. Eight articles were included, fulfilling our inclusion criteria, i.e., adult patients of ≥18 years with a recent diagnosis of acute MI. Pooled analysis was done using Review Manager version 5.4.1 (Cochrane Collaboration, London, England), and the data for each outcome were analyzed as dichotomous variables. A total of eight clinical trials were included in the meta-analysis. Six studies analyzed the sacubitril/valsartan and ACEI combination. The pooled analysis reported a significant increase in the risk of hypotension (relative risk {RR}: 1.29 {1.18, 1.41}) in the sacubitril/valsartan compared to the ACEI alone group. In addition, a significant increase was observed in the left ventricle ejection fraction (LVEF) after using the sacubitril/valsartan combination compared to using ACEI alone (RR: 3.08 {2.68, 4.48}). Furthermore, no significant difference was observed between the groups in terms of mortality rate (RR: 0.86 {0.73, 1.02}), the risk of heart failure (RR: 0.62 {0.39, 1.00}), the frequency of recurrent MI (RR: 0.86 {0.27, 2.76}), and the mean difference of N-terminal pro-B-type natriuretic peptide (NT-proBNP) (weighted mean difference {WMD}: -174.36 {-414.18, 65.46}) between both the groups. However, the sacubitril/valsartan combination proved to be beneficial in significantly reducing the risk of major adverse cardiac events (MACE) (RR: 0.64 {0.48, 0.84}) and rehospitalizations (RR: 0.53 {0.39, 0.71}) as compared to ACEI post MI. Additionally, sacubitril/valsartan and ARB's combination was reported in two studies. This led to a significant decrease in NT-proBNP concentration (WMD: -71.91 {-138.43, -5.39}) post MI in the sacubitril/valsartan combination group compared to the ARB usage alone. However, no significant difference was observed in the improvement of LVEF (WMD: 0.88 {-5.11, 6.87}) between both groups. Although the sacubitril/valsartan combination has no difference in mortality and outcomes compared to ACEI, there is evidence that using it proves to be more beneficial post MI compared to ACEI and ARB usage alone.

Synthesis of polycationic nanoparticles for microbial inhibition and killing.

Antimicrobial polymers (AMP) appear to be a promising candidate to deal with the current scenario of bacterial resistance against conventional drugs and antibiotics as they mainly depend on disrupting the bacterial membrane. This work investigates the effect of polycations bearing aromatic and aliphatic pendant cationic groups on the antimicrobial performance of AMP. A radical polymerization strategy was adopted to synthesize two different copolymers and convert them into polycations upon post-modification. Polyelectrolytes were converted into nanoparticles by nanoprecipitation and named PE1 and PE2. Polymers were analyzed by NMR, FT-IR, and gel permeation chromatography (GPC). PE1 and PE2 nanoparticles were uniform, spherical particles from FESEM, size, and zeta potential measurements. The antimicrobial properties of polyelectrolytes were determined against pathogenic Escherichia coli (E. coli), Bacillus Subtilis (B. Subtilis), Bacillus Amyloliquefaciens (B. Amyloliquefaciens) and Citrobecter Freundii (C. Freundii) bacterias. The biocidal activity determination studies showed that polyelectrolyte PE2 with aromatic pendant units outperformed PE1 with the aliphatic pendant group. This work highlights the remarkable effect of aromatic segmentation, which provides microbial inhibition, and killing is demonstrated as an antibacterial surface coating.