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Aldehyde dehydrogenase 1A3 (ALDH1A3) is a cancer stem cell marker that promotes metastasis. Triple‐negative breast cancer (TNBC) progression has been linked to ALDH1A3‐induced gene expression changes. To investigate the mechanism of ALDH1A3‐mediated breast cancer metastasis, we assessed the effect of ALDH1A3 on the expression of proteases and the regulators of proteases that degrade the extracellular matrix, a process that is essential for invasion and metastasis. This revealed that ALDH1A3 regulates the plasminogen activation pathway; it increased the levels and activity of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA). This resulted in a corresponding increase in the activity of serine protease plasmin, the enzymatic product of tPA and uPA. The ALDH1A3 product all‐trans‐retinoic acid similarly increased tPA and plasmin activity. The increased invasion of TNBC cells by ALDH1A3 was plasminogen‐dependent. In patient tumours, ALDH1A3 and tPA are co‐expressed and their combined expression correlated with the TNBC subtype, high tumour grade and recurrent metastatic disease. Knockdown of tPA in TNBC cells inhibited plasmin generation and lymph node metastasis. These results identify the ALDH1A3–tPA–plasmin axis as a key contributor to breast cancer progression.

CARP-1, a perinuclear phospho-protein, regulates cell survival and apoptosis signaling induced by genotoxic drugs. However, kinase(s) phosphorylating CARP-1 and down-stream signal transduction events remain unclear. Here we find that CARP-1 Serine (S)626 and Threonine (T)627 substitution to Alanines (AA) inhibits genotoxic drug-induced apoptosis. CARP-1 T627 is followed by a Proline (P), and this TP motif is conserved in vertebrates. Based on these findings, we generated affinity-purified, anti-phospho-CARP-1 T627 rabbit polyclonal antibodies, and utilized them to elucidate chemotherapy-activated, CARP-1-dependent cell growth signaling mechanisms. Our kinase profiling studies revealed that MAPKs/SAPKs phosphorylated CARP-1 T627. We then UV cross-linked protein extracts from Adriamycin-treated HeLa cervical cancer cells with a CARP-1 (614–638) peptide, and conducted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses of the peptide-bound protein complexes. This experiment revealed SAPK p38γ interaction with CARP-1 (614–638) peptide. Our studies further established that SAPK p38γ, but not other MAPKs, phosphorylates CARP-1 T627 in cancer cells treated with genotoxic drugs. Loss of p38γ abrogates CARP-1 T627 phosphorylation, and results in enhanced survival of breast cancer cells by genotoxic drugs. CARP-1 T627 phosphorylation was also noted in breast tumors from patients treated with radiation or endocrine therapies. We conclude that genotoxic drugs activate p38γ-dependent CARP-1 T627 phosphorylation to inhibit cell growth.

This study aims at simplifying the process of mix design of Self Compacting Concrete (SCC) which is generally done through trial and error. Concrete being a heterogeneous material, the desired qualities are attributed to several factors, in addition SCC has the requirement of better workability, which leads to the complexity in the design process. In this paper, the various factors affecting the strength and workability of SCC such as Total Cementitious Material (TCM) content, water-cementitious material ratio, percentage of fly ash replacement, coarse aggregate content and fine aggregate content were analyzed with four different values for each factor. Based on the Taguchi optimization method, an orthogonal array with sixteen experiments was designed to obtain the best factors for the SCC mix. The performance parameters selected were slump flow value for flowing ability, T5min of V funnel test for segregation resistance, L Box ratio for passing ability and compressive strength test for strength aspect. The results indicated that the TCM content and water-cementitious material ratio plays an important role in the workability of SCC, whereas TCM content and coarse aggregate content are predominant in the compressive strength of SCC. [ABSTRACT FROM AUTHOR]

This research studies self compacting concrete mixes with 0, 30, 40 and 50% fly ash as replacement which are internally cured with super absorbent polymer and lightweight expanded clay aggregates against Self Compacting Concrete which are conventionally cured by submerging in water for a specific period. The optimum dose of the Internal curing agent was determined based on the chemical shrinkage of cement paste and it was presoaked in the mixing water and incorporated at the time of mixing. Fresh properties like slump cone, V funnel and L box tests were made and the effect of fly ash and internal curing agent was reported. Properties like compressive strength and durability factors such as rate of water absorption and resistance to chloride penetration were studied. Also the relationship between compressive strength and chloride penetration was established. It was found that the addition of fly ash seems to be beneficial for self curing concrete specimens up to 40% in terms of strength and durability. Concrete internally cured with super absorbent polymer showed better performance when compared with concrete cured with clay aggregates. [ABSTRACT FROM AUTHOR]

Long non-coding RNA (lncRNA)/microRNA (miRNA)/messenger RNA (mRNA) interactions regulate oncogenesis and tumour suppression in breast cancer. Oncogenic lncRNA/miRNA/mRNA axes may offer novel therapeutic targets; therefore, identifying such axes is a clinically relevant undertaking. To explore miRNAs regulated by oncogenic lncRNAs, we queried the NCBI Gene Expression Omnibus (GEO) database to find datasets that profiled gene expression changes upon lncRNA knockdown in breast cancer. We identified four microarray datasets that permitted our interrogation of genes regulated by lncRNAs LincK, LincIN, SPRY4-IT1 and AC009283.1. We specifically analysed changes in miRNA transcripts within these datasets to study miRNAs regulated by each of the four lncRNAs. We subsequently identified the predicted mRNA targets for these miRNAs to uncover possible lncRNA/miRNA/mRNAs axes in breast cancer. These axes may be candidates for future investigation of gene regulation in breast cancer.

Vitamin D receptor (VDR) is a substrate for modification with small ubiquitin-like modifier (SUMO). To further assess the role of reversible SUMOylation within the vitamin D hormonal response, we evaluated the effects of sentrin/SUMO-specific proteases (SENPs) that can function to remove small ubiquitin-like modifier (SUMO) from target proteins upon the activities of VDR and related receptors. We report that SENP1 and SENP2 strikingly potentiate ligand-mediated transactivation of VDR and also its heterodimeric partner, retinoid X receptor (RXRα) with depletion of cellular SENP1 significantly diminishing the hormonal responsiveness of the endogenous vitamin D target gene CYP24A1. We find that SENP-directed modulation of VDR activity is cell line-dependent, achieving potent modulatory effects in Caco-2 and HEK-293 cells, while in MCF-7 cells the vitamin D signal is unaffected by any tested SENP. In support of their function as novel modulators of the vitamin D hormonal pathway we demonstrate that both SENP1 and SENP2 can interact with VDR and reverse its modification with SUMO2. In a preliminary analysis we identify lysine 91, a residue known to be critical for formation and DNA binding of the VDR-RXR heterodimer, as a minor SUMO acceptor site within VDR. In combination, our results support a repressor function for SUMOylation of VDR and reveal SENPs as a novel class of VDR/RXR co-regulatory protein that significantly modulate the vitamin D response and which could also have important impact upon the functionality of both RXR-containing homo and heterodimers.

This paper present a challenging case of a right ventricular mass in a patient who was at high surgical risk for open removal. The minimally invasive AngioVac device has been used with a successful 50% reduction in mass burden. This report illustrates AngioVac as a safe alternative to invasive surgery., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Acute pulmonary embolism (APE) is the third most common cause of vascular death. Data on APE from India and other low-and middle-income countries is sparse., Objectives: Study the clinical characteristics, prognostic factors, in-hospital mortality (IMH) and 12 months mortality of patients with APE in India., Methods: We prospectively enrolled 186 consecutive patients diagnosed with APE between November 2016 and November 2021 in Madras Medical College Pulmonary Embolism Registry (M-PER). All patients had electrocardiography and echocardiography. High risk patients and selected intermediate risk patients underwent fibrinolysis., Results: 75 % of our patients were below 50 years of age. 35 % were women. The mean time to presentation from symptom onset was 6.04 ± 10.01 days. 92 % had CT pulmonary angiography. Intermediate risk category (61.3 %) was the more common presentation followed by high risk (26.9 %). Electrocardiography showed S1Q3T3 pattern in 56 %. 76 % had right ventricular dysfunction and 12.4 % had right heart thrombi(RHT) by echocardiography. 50.5 % received fibrinolysis. Patients with RHT received fibrinolysis more frequently (78.3 % vs 46.6 %; p = 0.007). In-hospital mortality (IHM) was 15.6 %. Systemic arterial desaturation and need for mechanical ventilation independently predicted IHM. Ten patients (5.3 %) were lost to follow up. One year mortality was 26.7 % (47/176). One year mortality of patients discharged alive was similar among high, intermediate and low risk groups(14.8 % vs 1.9 % vs 10.5 %; p = 0.891)., Conclusions: Patients with PE are often young and present late in India. The in-hospital and 12 months mortality were high. Low and intermediate risk groups had a high post discharge mortality similar to high risk patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: This study aimed to investigate the effect of fascial manipulation (FM) of the deep cervical fascia (DCF) and sequential yoga poses (SYP) on pain and function in individuals with mechanical neck pain (MNP)., Method: Following the predefined criteria, ninety-nine individuals with MNP were recruited, randomised, and assigned to either the intervention group (IG) (n = 51) or the control group (CG) (n = 48). Individuals in the IG received FM (4 sessions in 4 weeks) and the home-based SYP (4 weeks). The CG participants received their usual care (cervical mobilisation and thoracic manipulation (4 sessions in 4 weeks) along with unsupervised therapeutic exercises (4 weeks). The participants underwent baseline and weekly follow-up measurements of pain using a numerical pain rating scale (NPRS) and elbow extension range of motion (EEROM) during the upper limb neurodynamic test 1 (ULNT1). The baseline and the fourth session follow-up measurements of the patient-specific functional scale (PSFS) and fear-avoidance behavior Questionnaire (FABQ) were also taken., Results: A repeated-measures ANOVA was performed. There were statistically significant differences between the IG and CG on the NPRS third and fourth sessions, with mean differences (MD) of -1.009 ( p < 0.05) and -1.701 ( p < 0.001), respectively. Regarding EEROM, there was a 20.120° difference ( p < 0.001) in the fourth session between the groups. The MD in FABQ was -5.036 ( p < 0.001), but there were no significant differences in PSFS between the groups during the follow-up., Conclusion: FM and SYP can aid in reducing pain and fear-avoidance behaviour and improve the function and extensibility of the upper quarter region.

Introduction: The aim of the study was to assess the presence and extent of sclerotic dentin and to study its impact on the direction of fracture lines in extracted mandibular first molars of young (20-44 years) and older age groups (45 and older)., Methods: Extracted permanent mandibular first molars were collected along with the related demographic details. A total of 40 teeth were included in this study, 20 each from young age group (YA group) (20-44 years) and older age group (OA group) (45-70 years). All molars were decoronated, and the sectioned mesial roots were embedded in acrylic blocks. They were subjected to vertical force in a universal testing machine. Fractured roots were then examined under the stereomicroscope at ×8 magnification to determine the direction and pattern of the fracture line. The roots were then sectioned and evaluated at ×10 and ×20 magnification to assess the dentin microstructure and its correlation with the direction of the fracture line. Statistical analysis was done by using χ 2 test (P < .05)., Results: A greater incidence and degree of sclerotic dentin were found in the OA group as compared with the YA group, which was statistically significant. The sclerotic dentin was distributed predominantly mesiodistally and the fracture line propagated buccolingually in both young and older groups, which was statistically significant (P < .05)., Conclusions: The presence of sclerotic dentin mesiodistally may impede crack propagation in this direction for both young and older age groups, causing the fracture line to extend buccolingually in coronal third of the root., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction  Orbital floor fractures are routinely encountered in facial trauma. Many factors influence the final outcome of the orbital floor surgery, time interval and the extent of other facial bone fractures are the two factors which can significantly influence the postoperative outcome following orbital floor reconstruction. Our study aims to find the ideal time for intervention and the association of other factors in the final outcome of orbital floor reconstruction. Methods  A retrospective and prospective cohort study of patients who were operated at Pondicherry Institute of Medical Sciences for orbital floor fractures, between 2011 January and 2017 July. All the data were entered on an Excel work sheet and statistically analyzed. Results  In our study 8 patients (8/29, 27.58%) had diplopia prior to surgery, 5 patients (5/29, 17.24%) had complete recovery following surgery and 3 patients (3/29, 10.34%) had persistence of diplopia postoperatively. Patients with diplopia operated prior to 7 days were found to have significant improvement in postoperative diplopia. Patients with 5 or more facial fractures were found to have persistence of diplopia, infraorbital numbness, and enophthalmos postoperatively. Conclusion  Our study suggests that early intervention, before 7 days improves the outcome in patients with diplopia and provides a better result postoperatively. In our study preoperative diplopia and infraorbital numbness and postoperative persistence of enophthalmos, diplopia, and paresthesia were found more in patients with 5 or more facial bone fractures. Our study suggests a poor postoperative outcome when 5 or more facial bones are fractured., Competing Interests: Conflict of Interest None declared., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Due to the proportionally high mortality rates associated with isolated tricuspid valve surgery, the invasive treatment of such pathology, historically, has been left largely unaddressed. Recently, there has been an appreciation for the mortality and morbidity of tricuspid valve disease, giving rise to the movement towards identifying less invasive, transcatheter approaches for treatment. Due to the technical complexity of these procedures along with the uniqueness and variability of tricuspid valve anatomy, a better appreciation of the tricuspid valve anatomy and pathology is required for pre-procedural planning. While two-dimensional echocardiography serves as the initial non-invasive modality for tricuspid valve evaluation, three-dimensional echocardiography provides a complete en face view of the tricuspid valve and surrounding structures, as well contributes further information regarding disease etiology and severity. In this review, we discuss the utility of three-dimensional echocardiography as a supplement to two-dimensional imaging to better assess tricuspid valve disease and anatomy to aide in future innovative therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Jost, Nooli, Ali, Jaganathan and Nanda.)

Tracheal tumor is a rare entity. Tracheal tumor may be a primary tracheal tumor or secondary to invasion from a mediastinal tumor (or a lymph node). These tumors are prone to cause critical airway obstruction which may require urgent care. Tuberculosis is one of the common differential diagnoses of mediastinal lymphadenopathy in TB endemic countries, though isolated tuberculous mediastinal lymphadenopathy without a lung involvement is rare. We report an extremely rare case of isolated paratracheal lymphadenitis due to tuberculosis, eroding the trachea and presented a lower tracheal tumor, which recurred again after complete debulking. Finally, the disease required a 'Y' stent placement, to stabilize the airway following the second recanalization. We discuss the incidence, differential diagnosis, and the bronchoscopic, interventional aspects of this entity.

Tender coconut water (TCW) is a natural plant product rich in phytochemicals and protects against toxic liver injury. However, the mechanism by which TCW inhibits inflammation and tissue damage is unknown. We examined the effect of TCW on primary rat hepatocyte viability, cytokine-induced gene expression and proinflammatory signaling in an in vitro model of sepsis. We observed that TCW improved hepatocyte viability and protected hepatocytes against cytokine-mediated cell death. TCW suppressed IL-1β-mediated increases in Nos2, Tnf, and Il6 mRNA and increased heme oxygenase 1 (HMOX1) protein. TCW inhibited iNOS expression through activation of AKT and JNK pathways since inhibition of PI3K and JNK signaling reduced TCW's effect on iNOS protein expression and activity. These results demonstrate that TCW reduces proinflammatory gene expression and hepatocyte injury produced by elevated inflammatory cytokines and nitric oxide production., Competing Interests: Conflict of interest: All authors declare no conflict of interest.

Pulmonary mucormycosis is a life-threatening invasive fungal infection usually seen in the background of immunosuppression, haematological malignancies, or uncontrolled diabetes. Immunocompetent hosts can also be affected. Isolated endobronchial mucormycosis is rare with only a few cases reported in the literature. Here, we present a case of an endobronchial mass masquerading as a tumour that was later diagnosed as invasive mucormycosis by histopathological examination., (© 2019 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Occupational heat stress apart from adverse heat-related health consequences also induces DNA damage in workers exposed to high working temperatures. We investigated the association between chronic heat exposures and Micronuclei (MN) frequency in lymphocytes of 120 workers employed in the steel industry. There was a significant increase in the MN-frequency in exposed workers compared to the unexposed workers (X 2  = 47.1; p < 0.0001) . While exposed workers had higher risk of DNA damage (Adj. OR = 23.3, 95% CI 8.0-70.8) compared to the unexposed workers, among the exposed workers, the odds of DNA damage was much higher for the workers exposed to high-heat levels (Adj. OR = 81.4; 95% CI 21.3-310.1) even after adjusting for confounders. For exposed workers, years of exposure to heat also had a significant association with higher induction of MN (Adj. OR = 29.7; 95% CI 2.8-315.5) . Exposures to chronic heat stress is a significant occupational health risk including damages in sub-cellular level, for workers. Developing protective interventions to reduce heat exposures is imperative in the rising temperature scenario to protect millions of workers across the globe., (© 2019 Informa UK Limited, trading as Taylor & Francis Group.)