Awareness data on cervical cancer among females of rural and urban areas of Haryana, India.

A cross-sectional study was done to assess the degree of current awareness and behaviors about cervical cancer among females in urban and rural areas of North India. This survey was conducted on one thousand females (500 rural and 500 urban). A well-structured questionnaire was designed to collect information about participants' knowledge on cancer of cervix uteri such as age, height and weight measurements, marital status, menstrual status, personal hygiene, age at menarche, sexual history, pregnancy and abortion history, use of contraceptive pills for birth-control, smoking, alcohol consumption, and other relevant information. The data was collected by conducting face-to-face interviews after obtaining the verbal consent of the participants. The data has the potential to reduce disease burden by spreading awareness about symptoms and risk factors of cervical cancer as well as implementation of effective early screening strategies.

Role of Amphotericin B in the Treatment of Mucormycosis.

BACKGROUND: Regardless of the most recent inclusion of mold-active agents (isavuconazole and posaconazole) to antifungal agents against mucormycosis, in conjunction with amphotericin B (AMB) items, numerous uncertainties still exist regarding the treatment of this rare infection. The order Mucorales contains a variety of fungi that cause the serious but uncommon fungal illness known as mucormycosis. The moulds are prevalent in nature and typically do not pose significant risks to people. Immunocompromised people are affected by it. OBJECTIVE: This article's primary goal is to highlight the integral role that AMB plays in this condition. METHODS: Like sinusitis (including pansinusitis, rhino-orbital, or rhino-cerebral sinusitis) is one of the many signs and symptoms of mucormycosis. The National Center for Biotechnology Information (NCBI) produces a variety of online information resources for review articles on the topic-based mucormycosis, AMB, diagnosis of mucormycosis and the PubMed® database of citations and abstracts published in life science journals. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov. RESULTS: The article provides a summary of the pharmacological attributes of the various AMB compositions accessible for systemic use. CONCLUSION: The article demonstrates the traits of the drug associated with its chemical, pharmacokinetics, stability, and other features, and illustrates their most useful characteristics for clinical application.

Overcoming multidrug resistance by reversan and exterminating glioblastoma and glioblastoma stem cells by delivering drug-loaded nanostructure hybrid lipid capsules (nHLCs).

Glioblastoma multiforme (GBM) is regarded as a highly aggressive brain cancer with a poor prognosis. There is an increase in the expression of P-glycoprotein (P-gp), responsible for multidrug resistance (MDR), making it a potential target for improving drug responses. Additionally, glioblastoma stem cells (GSCs) increase resistance to chemo- and radiotherapy and play a major role in cancer relapse. In this study, we targeted P-gp using a small molecule inhibitor, reversan (RV), to inhibit MDR that prolonged the retention of drugs in the cytosolic milieu. To eliminate GBM and GSCs, we have used two well-established anti-cancer drugs, regorafenib (RF) and curcumin (CMN). To improve the pharmacokinetics and decrease systemic delivery of drugs, we developed nanostructure hybrid lipid capsules (nHLCs), where hydrophobic drugs can be loaded in the core, and their physicochemical properties were determined by dynamic light scattering (DLS) and cryo-scanning electron microscopy (SEM). Inhibition of MDR by RV has also shown enhanced retention of nHLC in GBM cells. Co-delivery of drug-loaded nHLCs, pre-treated with RV, exhibited superior cytotoxicity in both GBM and GSCs than their individual doses and effectively reduced the size and stemness of tumor spheres and accelerated the rate of apoptosis, suggesting a promising treatment for glioblastoma.

Caesarean scar ectopic pregnancy: A case series.

Caesarean scar ectopic pregnancy (CSEP) is a uncommon presentation of pregnancy with incidence of nearly 1 in 2000 pregnancies. We present this case series of scar pregnancy with a objective to help obstetricians in early diagnosis and appropriate management to prevent its catastrophic complications.

pH-Responsive Polypropylene Sulfide Magnetic Nanocarrier-Mediated Chemo-Hyperthermia Kills Breast Cancer Stem Cells by Long-Term Reversal of Multidrug Resistance and Chemotherapy Resensitization.

Cancer stem cells (CSCs) present a formidable challenge in cancer treatment due to their inherent resistance to chemotherapy, primarily driven by the overexpression of ABC transporters and multidrug resistance (MDR). Despite extensive research on pharmacological small-molecule inhibitors, effectively managing MDR and improving chemotherapeutic outcomes remain elusive. On the other hand, magnetic hyperthermia (MHT) holds great promise as a cancer therapeutic, but there is limited research on its potential to reverse MDR in breast CSCs and effectively eliminate CSCs through combined chemo-hyperthermia. To address these gaps, we developed tumor microenvironment-sensitive, drug-loaded poly(propylene sulfide) (PPS)-coated magnetic nanoparticles (PPS-MnFe). These nanoparticles were employed to investigate hyperthermia sensitivity and MDR reversion in breast CSCs, comparing their performance to that of small-molecule inhibitors. Additionally, we explored the efficacy of combined chemo-hyperthermia in killing CSCs. CSC-enriched breast cancer cells were subjected to low-dose MHT at 42 °C for 30 min and then treated with the chemical MDR inhibitor salinomycin (SAL). The effectiveness of each treatment in inhibiting MDR was assessed by measuring the efflux of the MDR substrate, rhodamine 123 (R123) dye. Notably, MHT induced a prolonged reversal of MDR activity compared with SAL treatment alone. After successfully inhibiting MDR, the breast CSCs were exposed to chemotherapy using paclitaxel to trigger synergistic cell death. The combination of MHT and chemotherapy demonstrated remarkable reductions in stemness properties, MDR reversal, and the effective eradication of breast CSCs in this innovative dual-modality approach.

Artificial Intelligence for Computer-Aided Drug Discovery.

The continuous implementation of Artificial Intelligence (AI) in multiple scientific domains and the rapid advancement in computer software and hardware, along with other parameters, have rapidly fuelled this development. The technology can contribute effectively in solving many challenges and constraints in the traditional development of the drug. Traditionally, large-scale chemical libraries are screened to find one promising medicine. In recent years, more reasonable structure-based drug design approaches have avoided the first screening phases while still requiring chemists to design, synthesize, and test a wide range of compounds to produce possible novel medications. The process of turning a promising chemical into a medicinal candidate can be expensive and time-consuming. Additionally, a new medication candidate may still fail in clinical trials even after demonstrating promise in laboratory research. In fact, less than 10% of medication candidates that undergo Phase I trials really reach the market. As a consequence, the unmatched data processing power of AI systems may expedite and enhance the drug development process in four different ways: by opening up links to novel biological systems, superior or distinctive chemistry, greater success rates, and faster and less expensive innovation trials. Since these technologies may be used to address a variety of discovery scenarios and biological targets, it is essential to comprehend and distinguish between use cases. As a result, we have emphasized how AI may be used in a variety of areas of the pharmaceutical sciences, including in-depth opportunities for drug research and development.

Design and synthesis of photostable triphenylamine based neutral AIE nano luminogens: specific and long-term tracking of mitochondria in cells.

With the increasing dependence on fluorescence bioimaging, luminogens with aggregation-induced emission (AIE) properties have gained significant attention due to their excellent photostabilization, minimal photobleaching, high reliability, and superior biocompatibility. Since mitochondria are crucial subcellular organelles in eukaryotic cells with important biological functions, organelle-specific AIE emitters with distinct functions have been highly sought after, but with limited success using simple synthetic methods. Here, we describe a strategy for synthesizing two triphenylamine (TPA) based acrylonitriles, tethered to different donor groups, TPA and phenothiazine (PTZ), respectively, with superior AIE properties using Suzuki coupling. We conducted a systematic and detailed experimental analysis of the structural characteristics of both AIE luminogens, which exhibited excellent photostability, a large Stokes shift, and bright solid-state emission. A cell viability study carried out with F1 and F2 dyes revealed that both luminogens exhibited excellent biocompatibility. Based on fluorescence experiments, F2 displayed excellent AIE characteristics, permeability, biocompatibility, and photostability compared to rhodamine 123, allowing it to selectively stain and track mitochondria in cancer cells over an extended period of time. The Pearson correlation coefficient of F2 and rhodamine 123 was estimated to have an r-value of 0.99. Our findings are expected to provide insight into the synthesis of an extensive archive of AIE-based acrylonitriles with fascinating properties for mitochondrial staining.

Long non-coding RNAs as critical regulators and novel targets in cervical cancer: current status and future perspectives.

Cervical cancer is among the leading causes of cancer-associated mortality in women. In spite of vaccine availability, improved screening procedures, and chemoradiation therapy, cervical cancer remains the most commonly diagnosed cancer in 23 countries and the leading cause of cancer deaths in 36 countries. There is, therefore, a need to come up with novel diagnostic and therapeutic targets. Long non-coding RNAs (lncRNAs) play a remarkable role in genome regulation and contribute significantly to several developmental and disease pathways. The deregulation of lncRNAs is often observed in cancer patients, where they are shown to affect multiple cellular processes, including cell cycle, apoptosis, angiogenesis, and invasion. Many lncRNAs are found to be involved in the pathogenesis as well as progression of cervical cancer and have shown potency to track metastatic events. This review provides an overview of lncRNA mediated regulation of cervical carcinogenesis and highlights their potential as diagnostic and prognostic biomarkers as well as therapeutic targets for cervical cancer. In addition, it also discusses the challenges associated with the clinical implication of lncRNAs in cervical cancer.

Biomaterial-based platforms for modulating immune components against cancer and cancer stem cells.

Immunotherapy involves the therapeutic alteration of the patient's immune system to identify, target, and eliminate cancer cells. Dendritic cells, macrophages, myeloid-derived suppressor cells, and regulatory T cells make up the tumor microenvironment. In cancer, these immune components (in association with some non-immune cell populations like cancer-associated fibroblasts) are directly altered at a cellular level. By dominating immune cells with molecular cross-talk, cancer cells can proliferate unchecked. Current clinical immunotherapy strategies are limited to conventional adoptive cell therapy or immune checkpoint blockade. Targeting and modulating key immune components presents an effective opportunity. Immunostimulatory drugs are a research hotspot, but their poor pharmacokinetics, low tumor accumulation, and non-specific systemic toxicity limit their use. This review describes the cutting-edge research undertaken in the field of nanotechnology and material science to develop biomaterials-based platforms as effective immunotherapeutics. Various biomaterial types (polymer-based, lipid-based, carbon-based, cell-derived, etc.) and functionalization methodologies for modulating tumor-associated immune/non-immune cells are explored. Additionally, emphasis has been laid on discussing how these platforms can be used against cancer stem cells, a fundamental contributor to chemoresistance, tumor relapse/metastasis, and failure of immunotherapy. Overall, this comprehensive review strives to provide up-to-date information to an audience working at the juncture of biomaterials and cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Cancer immunotherapy possesses incredible potential and has successfully transitioned into a clinically lucrative alternative to conventional anti-cancer therapies. With new immunotherapeutics getting rapid clinical approval, fundamental problems associated with the dynamic nature of the immune system (like limited clinical response rates and autoimmunity-related adverse effects) have remained unanswered. In this context, treatment approaches that focus on modulating the compromised immune components within the tumor microenvironment have garnered significant attention amongst the scientific community. This review aims to provide a critical discussion on how various biomaterials (polymer-based, lipid-based, carbon-based, cell-derived, etc.) can be employed along with immunostimulatory agents to design innovative platforms for selective immunotherapy directed against cancer and cancer stem cells.

Polypropylene sulphide coating on magnetic nanoparticles as a novel platform for excellent biocompatible, stimuli-responsive smart magnetic nanocarriers for cancer therapeutics.

Magnetic nanoparticle (MNP) delivery systems are promising for targeted drug delivery, imaging, and chemo-hyperthermia of cancer; however, their uses remain limited primarily due to their toxicity associated with reactive oxygen species (ROS) generation, targeted delivery, and biodegradation. Attempts employing polymer coatings to minimize the toxicity, along with other challenges, have had limited success. We designed a novel yet generic 'one-for-all' polypropylene sulphide (PPS) coated magnetic nano-delivery system (80 ± 15 nm) as a multi-faceted approach for significant biocompatibility improvement, loading of multiple drugs, ROS-responsive delivery, and combined chemo-hyperthermia therapy for biomedical applications. Three distinct MNP systems (15 ± 1 nm) were fabricated, coated with PPS polymer, and investigated to validate our hypothesis and design. Simultaneous degradation of MNPs and PPS coatings with ROS-scavenging characteristics boosted the biocompatibility of MNPs 2-3 times towards non-cancerous fibroblasts (NIH3T3) and human epithelial cells (HEK293). In an alternating magnetic field, PPS-MNPs (MnFe) had the strongest heating characteristics (SAR value of 240 W g-1). PPS-MNP drug-loaded NPs were efficiently internalised into cells and released 80% of the drugs under tumor microenvironment-mimicking (pH 5-7, ROS) conditions, and demonstrated effective chemo-hyperthermia (45 °C) application for breast cancer cells with 95% cell death in combined treatment vs. 55% and 30% cell death in only hyperthermia and chemotherapy respectively.

Successful management of cervical dysgenesis: Case report and review.

Cervical agenesis or dysgenesis is a rare Mullerian anomaly that is usually associated with vaginal aplasia. A literature review revealed reports of 83 cases including ours, of which 57 (68.6%) presented with obstruction of the external OS, 11 (13.2%) had the cervix replaced by a fibrous cord and 5 (6.02%) had a fragmented cervix. A total of 24 (28.9%) were managed by core and drilling technique (CDT), 16(19.2%) patients underwent uterovaginal anastomosis (UVA), 7(8.4%) underwent total abdominal hysterectomy preserving the ovaries and 5 (6.02%) were managed by cervical reconstruction. Unfortunately, 31 failed to return after their clinical and radiological diagnosis was confirmed. Early diagnosis and treatment are necessary to avoid long-term complications.

Fabrication, characterization and efficacy evaluation of natural gum-based bioactive haemostatic gauzes with antibacterial properties.

Management of uncontrolled bleeding due to traumatic injuries occurring in battlefields and road traffic accidents is a major healthcare concern, especially in developing countries like India. Since natural coagulation mechanism alone is insufficient to achieve haemostasis quickly in such cases, application of an external haemostatic product is generally required to accelerate the coagulation process. We had recently reported preliminary comparison of four natural absorbent gums, which indicated towards haemostatic potential of gum tragacanth (GT) and xanthan gum (XG). Present study involves fabrication of haemostatic dressings incorporated with different concentrations of GT or XG, along with ciprofloxacin (a broad-spectrum antibiotic) and other excipients over woven cotton gauze. Prepared gauzes were investigated for physico-chemical characteristics, in-vitro blood interaction studies, antibacterial effect and in-vivo haemostatic efficacy in Sprague Dawley rats using two bleeding models. Acute dermal toxicity studies were also carried out as per OECD guidelines. SEM studies showed that gauzes coated with XG had thin, uniform layer of coating, while in case of GT; coating was comparatively rough with insoluble particles of GT adhering over gauze surface, forming voids on the fibers. Coated gauzes exhibited optimum mechanical properties in terms of tensile strength and percent extension at break. GT coated dressings showed good fluid uptake and retention ability in-vitro. Test gauzes were non-hemolytic in nature, did not elicit any dermal toxicity on animals' skin and had the ability to protect against E. coli infection. In-vivo efficacy studies in rat femoral artery and liver laceration bleeding models indicated that gauzes coated with 4% GT were able to clot blood in least time (36.67 ± 3.33s and 40 ± 2.58s respectively) as compared to other gum combinations and commercially available dressing 'Surgispon® (103.3 ± 4.22s and 85 ± 5.62s respectively). Results of this study validate our initial findings of the potential of gum tragacanth to be developed into a suitable haemostatic product.

Effect of Propranolol Prophylaxis on Headache Frequency in Children with Migraine Without Aura: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To compare the efficacy of propranolol prophylaxis with placebo on headache frequency in children with migraine over the 3-mo follow-up. METHODS: In this randomized, double-blind, placebo-controlled trial children aged 6-12 y with newly diagnosed migraine without aura as per the International Classification for Headache Disorders, 3rd edition (ICHD-3) criteria were enroled. They were randomized to the intervention group receiving oral propranolol (1-3 mg/kg/d, BID) and the control group receiving a similar looking, inert, oral placebo for migraine prophylaxis for 3 mo. The number of migraine attacks over the 3-mo follow-up (using a headache diary) was the primary outcome. Pediatric Migraine Disability Assessment Scale (PedMIDAS) was used for assessing disability and Visual analogue scale was used for assessing headache severity. Analysis was done on intention-to-treat basis. RESULTS: Twenty children (10 in each group) completed the study. The two groups were similar at baseline. Both the study drugs produced significant reduction of headache frequency after the study intervention (p = 0.002). However, there was no difference between the two groups with respect to either the median (IQR) number of headache attacks [22 (20, 25) vs. 14 (10, 20); p = 0.05], headache severity [1 (0, 1) vs. 0.5 (0, 1); p = 0.48] or migraine disability [39.5 (28, 44) vs. 35 (22, 38); p = 0.27]. Adverse effects were higher in the intervention group (p = 0.52). CONCLUSIONS: Propranolol was effective for migraine prophylaxis in children but the effect was not higher than placebo. Larger placebo-controlled trials of propranolol need to be conducted to decide its place in migraine prophylaxis in children. TRIAL REGISTRATION: Thailand Clinical Trials Registry; TCTR20200621001.

Ultrashort Peptide-Based Hydrogel for the Healing of Critical Bone Defects in Rabbits.

The use of hydrogels as scaffolds for three-dimensional (3D) cell growth is an active area of research in tissue engineering. Herein, we report the self-assembly of an ultrashort peptide, a tetrapeptide, Asp-Leu-IIe-IIe, the shortest peptide sequence from a highly fibrillogenic protein TDP-43, into the hydrogel. The hydrogel was mechanically strong and highly stable, with storage modulus values in MPa ranges. The hydrogel supported the proliferation and successful differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in its matrix as assessed by cell viability, calcium deposition, alkaline phosphatase (ALP) activity, and the expression of osteogenic marker gene studies. To check whether the hydrogel supports 3D growth and regeneration in in vivo conditions, a rabbit critical bone defect model was used. Micro-computed tomography (CT) and X-ray analysis demonstrated the formation of mineralized neobone in the defect areas, with significantly higher bone mineralization and relative bone densities in animals treated with the peptide hydrogel compared to nontreated and matrigel treatment groups. The ultrashort peptide-based hydrogel developed in this work holds great potential for its further development as tissue regeneration and/or engineering scaffolds.

Biomimicking nanofibrous gelatin microspheres recreating the stem cell niche for their ex-vivo expansion and in-vivo like differentiation for injectable stem cell transplantation.

Stem cells based novel treatment modality for degenerative and immune dysfunction diseases created a huge demand of suitable carriers to support ex-vivo production of quality stem cells, and effective in-vivo transplantation of stem cells and their fate. In spite of promising candidature of nanofibrous microspheres (NFM) to recreate native stem cell niches to be used for possible scaling-up for ex-vivo stem cells expansion, it remains fairly unexplored. A systematic study on the stem cell-NFM interaction comparative with commercial microspheres (CM) has been performed for the first time. Gelatin NFM with variable physicochemical properties such as size, surface properties, surface chemistry, and variable degradability were prepared using microemulsion coupled with thermally induced phase separation (TIPS) method. Effect of physicochemical properties of NFM and their cellular interaction such as binding, morphology, metabolic activity and proliferation studies were performed using human bone marrow-derived mesenchymal stem cells (hBMSCs), human dental follicle stem cells (hDFSCs) and human gingival fibroblast (HGF) cells and compared with the commercial and solid microspheres. Gelatin NFM supports excellent cell binding, proliferation, metabolic activities and chemical cues specific differentiation. All out-turns indicate that NFM stand to be an outstanding candidate for ex-vivo cells' expansion and injectable carriers for stem cell transplantation.

Diagnosis of genitourinary tuberculosis by loop-mediated isothermal amplification based on SYBR Green I dye reaction.

A multitargeted loop-mediated isothermal amplification (MT-LAMP) assay targeting mpt64 (Rv1980c) and IS6110 was designed to diagnose genitourinary tuberculosis (GUTB) cases. While assessing gel-based, hydroxynaphthol blue (HNB) and SYBR Green I MT-LAMP assays on GUTB specimens (n = 28) in a pilot study, both gel-based/SYBR Green I assays exhibited better sensitivity than HNB LAMP. Since SYBR Green MT-LAMP is easier to perform compared with a gel-based assay, a higher number of GUTB specimens (n = 55) were evaluated by SYBR Green MT-LAMP, wherein 85.5% sensitivity and 94.4% specificity (n = 36) were obtained. Moreover, the sensitivity attained by MT-LAMP was significantly higher (p < 0.05) than with multiplex-PCR (mpt64 + IS6110). After further validating these MT-LAMP data in different epidemiological settings, this assay may be developed as a diagnostic kit.

Quantitative evaluation of mercury adsorption and removal efficacy of Spirulina (Arthrospira platensis) powder in mice.

Spirulina is a blue-green alga, grown in alkaline water and used for detoxification of several toxic metal ions. Apart from its nutritional value, it is also used for the decontamination of toxic metal ions. Therefore, present study was envisaged to evaluate the adsorption and removal efficiency of Spirulina powder for mercury. The adsorption efficiency of Spirulina was evaluated in terms of weight of adsorbent, contact time, simulated gastric (SGF) and intestinal (SIF) fluid, and mercury concentration. In vivo removal efficacy of Spirulina for mercury was evaluated in mice. The mercury content in major tissues, urine and feces was estimated. The whole tissue retention and excretion of mercury after treatment with Spirulina were taken as a measure of its metal ions removal efficacy. Activated charcoal was taken as a standard adsorbent for comparative study. The maximum adsorption capacity of Spirulina and charcoal for mercury was found to be 66.667 and 158.730 mg g-1 in water, 83.33 and 94.340 mg g-1 in SGF and 125.0 and 133.33 mg g-1 in SIF, respectively. In mice, Spirulina and activated charcoal were significantly reduced the mercury deposition in tissues and facilitated their excretion through feces. Spirulina has shown good adsorption and removal efficacy like activated charcoal. Therefore, Spirulina can be used as a potential adsorbent to remove mercury from the body.

Renal Outcomes of Pregnancy-Related Acute Kidney Injury: a Single Centre Experience in India.

Objective:This study aimed to investigate the incidence, clinical characteristics, and outcomes of acute kidney injury (AKI) during pregnancy in Indian population. Materials and methods:A prospective observational study was conducted in pregnant patients admitted to Pt. B.D. Sharma PGIMS, Rohtak, Haryana, India. Acute kidney injury was assessed using Risk, Injury, Failure, Loss of function, and End-stage renal disease (RIFLE) criteria. Patients were analyzed on the basis of demographic data, detailed history, clinical examination, and laboratory investigations. The primary outcome was maternal renal outcome, including return to normal renal function and progression to chronic kidney disease (CKD). The secondary outcomes included the mode of delivery, complications of pregnancy, intensive care unit (ICU) admission, and maternal death. Results:A total of 51 patients with an average age of 29.5 years were included in the present study. About 49.9% of subjects had severe anemia and 41.2% were primigravida. The main cause of AKI was pre-eclampsia and postpartum hemorrhage. There was a marked improvement in renal outcome with 33 patients having complete renal recovery and six patients developed CKD was observed during three months follow-up period. The peaked median value of blood urea was 62.0 mg% in patients with normal renal function, 178.5 mg% in those with CKD and 120.0 mg% in expired patients (P=0.001). A statistically significant change in serum potassium (P=0.010) and creatinine levels (P<0.001) was observed during the follow-up period. Liver enzymes, including serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase, were high in all patients at the time of admission, but decreased to normal on follow-up. Conclusion:Our study indicates that pregnancy-related AKI patients present with multiorgan complications and many of them require mechanical ventilation and renal replacement therapy. Most of these patients have poor outcome. Hence, the management of pregnancy-related AKI presents a challenge that requires proper evaluation of causative factors to facilitate appropriate treatment.