Non-coding RNA mediated regulation of PI3K/Akt pathway in hepatocellular carcinoma: Therapeutic perspectives.

Hepatocellular carcinoma (HCC) is among the primary reasons for fatalities caused by cancer globally, highlighting the need for comprehensive knowledge of its molecular aetiology to develop successful treatment approaches. The PI3K/Akt system is essential in the course of HCC, rendering it an intriguing candidate for treatment. Non-coding RNAs (ncRNAs), such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are important mediators of the PI3K/Akt network in HCC. The article delves into the complex regulatory functions of ncRNAs in influencing the PI3K/Akt system in HCC. The study explores how lncRNAs, miRNAs, and circRNAs impact the expression as well as the function of the PI3K/Akt network, either supporting or preventing HCC growth. Additionally, treatment strategies focusing on ncRNAs in HCC are examined, such as antisense oligonucleotide-based methods, RNA interference, and small molecule inhibitor technologies. Emphasizing the necessity of ensuring safety and effectiveness in clinical settings, limitations, and future approaches in using ncRNAs as therapies for HCC are underlined. The present study offers useful insights into the complex regulation system of ncRNAs and the PI3K/Akt cascade in HCC, suggesting possible opportunities for developing innovative treatment approaches to address this lethal tumor.

Perampanel as monotherapy or first adjunctive therapy in pediatric and adult patients with epilepsy: the first United States-based phase IV open-label ELEVATE study.

ELEVATE (Study 410; NCT03288129) is the first prospective, multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with focal-onset seizures or generalized tonic-clonic seizures in the United States. The study included Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration, perampanel was initiated at 2 mg/day and up-titrated to 4 mg/day at Week 3. Depending on response and tolerability, optional up-titrations to a maximum of 12 mg/day occurred. The primary endpoint was retention rate; additional endpoints included seizure-freedom rate, 50% responder rate, and incidence of treatment-emergent adverse events (TEAEs). At baseline, 10 (18.5%) patients were assigned to the monotherapy group and 44 (81.5%) patients to the first adjunctive therapy group. However, due to the addition of an anti-seizure medication along with perampanel on the first day of treatment, one patient was excluded from the monotherapy subgroup analyses. The mean perampanel exposure duration was 39.8 weeks and 32 (59.3%) patients completed the study. Retention rate at 12 months (or study completion) was 63.0% (monotherapy, 77.8%; first adjunctive therapy, 59.1%). Seizure-freedom rate during the Maintenance Period was 32.7% (monotherapy, 44.4%; first adjunctive therapy, 29.5%) and the 50% responder rate was 78.7% (monotherapy, 85.7%; first adjunctive therapy, 76.9%). TEAEs and serious TEAEs were reported by 88.9% (n = 48/54) and 7.4% (n = 4/54) of patients, respectively. Overall, the efficacy and safety of perampanel as monotherapy or first adjunctive therapy support the use of perampanel as early-line treatment for epilepsy.

Mapping Neurophysiological Patterns in Carpal Tunnel Syndrome: Correlations With Tinel's and Phalen's Signs.

Background This study aimed to observe the neurophysiological severity grading of carpel tunnel syndrome (CTS) using nerve conduction studies (NCSs) and the correlation between Tinel's and Phalen's signs. Methodology In this cross-sectional study, 240 patients of CTS were enrolled. NCSs were conducted in 480 hands. Various variables such as distal latency, amplitude, and nerve conduction velocity in both sensory and motor median nerves were recorded. The provocative tests capable of reproducing patients' symptoms such as Phalen's test and Tinel's test were performed on all 480 hands studied. Results Neurophysiological variables were affected in 449 out of 480 hands. Tinel's sign was observed in 59% of cases (265 hands) while Phalen's sign was positive in 37.2% (167 hands) of cases. Severity grading of CTS based on neurophysiological variables resulted in Grade I (mild) in 202 hands, Grade II (mild to moderate) in 56 hands, Grade III (moderate) in 39 hands, and Grade IV (severe) in 152 hands. Provocative tests (Tinel's and Phalen's) used for the diagnosis of CTS were positive in 68 hands (36.66%) and 26 hands (12.8%), respectively, in mild Grade I. However, as the CTS severity grade increased, the provocative test success rate also increased simultaneously. In severe Grade IV CTS, Tinel's and Phalen's tests were positive in 134 (88.1%) hands and 94 (61.8%) hands, respectively. Conclusions This study underscores the unreliability of Tinel's and Phalen's signs as screening methods for CTS severity. With moderate sensitivity and specificity, NCSs are deemed essential for confirming CTS diagnosis and assessing severity, especially in mild cases that might be mistakenly perceived as normal hands by consultants.

Facial expressions to identify post-stroke: A pilot study.

BACKGROUND AND OBJECTIVE: Timely stroke treatment can limit brain damage and improve outcomes, which depends on early recognition of the symptoms. However, stroke cases are often missed by the first respondent paramedics. One of the earliest external symptoms of stroke is based on facial expressions. METHODS: We propose a computerized analysis of facial expressions using action units to distinguish between Post-Stroke and healthy people. Action units enable analysis of subtle and specific facial movements and are interpretable to the facial expressions. The RGB videos from the Toronto Neuroface Dataset, which were recorded during standard orofacial examinations of 14 people with post-stroke (PS) and 11 healthy controls (HC) were used in this study. Action units were computed using XGBoost which was trained using HC, and classified using regression analysis for each of the nine facial expressions. The analysis was performed without manual intervention. RESULTS: The results were evaluated using leave-one-our validation. The accuracy was 82% for Kiss and Spread, with the best sensitivity of 91% in the differentiation of PS and HC. The features corresponding to mouth muscles were most suitable. CONCLUSIONS: This pilot study has shown that our method can detect PS based on two simple facial expressions. However, this needs to be tested in real-world conditions, with people of different ethnicities and smartphone use. The method has the potential for a computerized assessment of the videos for use by the first respondents using a smartphone to perform screening tests, which can facilitate the timely start of the treatment.

Unveiling novel metabolic alterations in postmenopausal osteoporosis and type 2 diabetes mellitus through NMR-based metabolomics: A pioneering approach for identifying early diagnostic markers.

BACKGROUND AND AIMS: Postmenopausal osteoporosis (PMO) and type 2 diabetes mellitus (T2DM) frequently coexist in postmenopausal women. The study aimed to explore metabolic variations linked to these circumstances and their simultaneous presence through proton nuclear magnetic resonance metabolomics (1H NMR). MATERIALS AND METHODS: Serum samples from 80 postmenopausal women, including 20 PMO individuals, 20 T2DM, 20 T2DM + PMO, and 20 healthy postmenopausal women, were analyzed using 1H NMR spectroscopy. RESULTS: Our study revealed significant metabolic profile differences among the four groups. Notably, the T2DM + PMO group showed elevated levels of alanine, pyruvate, glutamate, lactate, and aspartate, indicating their involvement in lipid metabolism, energy, and amino acids. Importantly, our multivariate statistical analysis identified a metabolite set that accurately distinguished the groups, suggesting its potential as an early diagnostic marker. CONCLUSION: The 1H NMR metabolomics approach uncovered metabolic biomarkers intricately linked to postmenopausal osteoporosis (PMO), type 2 diabetes mellitus (T2DM), and their concurrent presence. Among these biomarkers, alanine emerged as a pivotal player, showing its significant role in the metabolic landscape associated with PMO and T2DM. These findings shed light on the pathophysiological mechanisms underlying these conditions and underscore alanine's potential as a diagnostic biomarker.

Review on novel targeted enzyme drug delivery systems: enzymosomes.

The goal of this review is to present enzymosomes as an innovative means for site-specific drug delivery. Enzymosomes make use of an enzyme's special characteristics, such as its capacity to accelerate the reaction rate and bind to a particular substrate at a regulated rate. Enzymosomes are created when an enzyme forms a covalent linkage with a liposome or lipid vesicle surface. To construct enzymosomes with specialized activities, enzymes are linked using acylation, direct conjugation, physical adsorption, and encapsulation techniques. By reducing the negative side effects of earlier treatment techniques and exhibiting efficient medication release, these cutting-edge drug delivery systems improve long-term sickness treatments. They could be a good substitute for antiplatelet medication, gout treatment, and other traditional medicines. Recently developed supramolecular vesicular delivery systems called enzymosomes have the potential to improve drug targeting, physicochemical characteristics, and ultimately bioavailability in the pharmaceutical industry. Enzymosomes have advantages over narrow-therapeutic index pharmaceuticals as focusing on their site of action enhances both their pharmacodynamic and pharmacokinetic profiles. Additionally, it reduces changes in normal enzymatic activity, which enhances the half-life of an enzyme and accomplishes enzyme activity on specific locations.

Organs-specific metabolomics and anticholinesterase activity suggests a trade-off between metabolites for therapeutic advantages of Trillium govanianum Wall. ex D. Don.

Trillium govanianum is traditionally used to treat innumerable alignments like sexual disorders, cancer, inflammation etc. Mainly rhizomes of T. govanianum have been explored for phytochemical profiling but comprehensive metabolomics of other parts has not been yet deeply investigated. Thus, current study was aimed for organs-specific (roots, rhizomes, rhizomatous buds, stems, leaves, and fruits) phytochemical profiling of T. govanianum via metabolomics approach. Targeted (steroidal saponins and free sugars) and non-targeted metabolomics were performed by UPLC-PDA/ELSD & UHPLC-Q-TOF-IMS. Among steroidal compounds, 20-hydroxyecdysone, pennogenin-3-O-ß-chacotrioside, dioscin were found predominantly in all samples while diosgenin was identified only in rhizomes. Further, four free sugars viz. 2-deoxyribose (116.24 ± 1.26 mg/g: leaves), fructose (454.76 ± 12.14 mg/g: rhizomes), glucose (243.21 ± 7.53 mg/g: fruits), and galactose (69.06 ± 2.14 mg/g: fruits) were found significant in respective parts of T. govanianum. Elemental analysis of targeted samples was determined by atomic absorption spectrophotometer. Heavy metals (Cd, Hg, Pd, As) were absent while micro- (Mn, Na, Zn, Cu) and macro- (Ca, Fe, Mg, K) elements were found in all samples. Furthermore, UHPLC-Q-TOF-IMS had identified 103 metabolites based on their mass fragmentation patterns and 839 were tentatively predicted using METLIN database. The multivariate statistical analysis showed organs specific clustering and variance of metabolites. Apart from this, extracts were evaluated for in vitro anticholinesterase activity, and found potentials inhibitors with IC50 values 2.02 ± 0.15 to 27.65 ± 0.89 mg/mL and 3.58 ± 0.12 to 16.81 ± 2.48 mg/mL of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme, respectively. Thus, comprehensive metabolomics and anti-cholinesterase activity of different parts of T. govanianum would lay the foundation for improving medicinal importance and health benefits of T. govanianum.

Chitosan-TPP encapsulated quercetin nanoparticles: amplified protection mechanisms unveiled against Ethion-induced developmental toxicity through comprehensive in-vivo and in-silico elucidation.

Aim: The study investigated Ethion-induced developmental toxicity in Wistar albino rats and the potential ameliorative effects of quercetin and nano-quercetin co-administration. Further, In-silico docking of Ethion and quercetin with MCL-1 was conducted. Methodology: Quercetin nanoparticles were synthesized by ionic-gelation method. The encapsulated quercetin nanoparticles were characterized for Zeta size, UV-Vis spectroscopy, encapsulation efficiency, and TEM studies. Male rats were administered Ethion (high/low dose), quercetin, and nano-quercetin alone or in combination for 60 days. Female rats were introduced for mating on the 61st day, and pregnant females were observed for 20 gestational days. On GD 20, rats were sacrificed and evaluated for body/organ weight, reproductive indices, fetal morphology, skeletal, and visceral deformities.In silico binding energies of ethion and quercetin with MCL-1 were determined. Results: Nanoparticle size was 363.2 ± 1.23 nm on day 0 and 385.63 ± 1.53 nm on day 60, with PDI of 0.247 and charge of 22.9 mV. Absorbance maxima were at 374 nm, with encapsulation efficacy of 85.16 ± 0.33%. EHD male crossed females showed decreased body/organ weights, reduced fertility, hematoma, cleft palate, tail curling, and absence of extremity. Nano-quercetin co-administration normalized parameters comparable to controls. Both Ethion and quercetin interacted with MCL-1, with quercetin exhibiting stronger binding energy. Conclusion: Nano-quercetin demonstrated stronger antioxidant properties than quercetin, counteracting ethion-induced maternal/fetal abnormalities.

Enhanced Therapeutic Efficacy Against Melanoma through Exosomal Delivery of Hesperidin.

Melanoma, characterized as the most aggressive and metastatic form of skin cancer, currently has limited treatment options, predominantly chemotherapy and radiation therapy. However, the drawbacks associated with parenterally administered chemotherapy underscore the urgent need for alternative compounds to combat melanoma effectively. Hesperidin (HES), a flavonoid present in various citrus fruits, exhibits promising anticancer activity. Nevertheless, the clinical utility of HES is hindered by challenges such as poor water solubility, a short half-life, and low oral bioavailability. In response to these limitations, we introduced a novel approach by formulating HES-loaded exosomes (Exo-HES). Isolation of exosomes was achieved through the ultracentrifugation method, and HES was efficiently loaded using the sonication method. The resulting formulations displayed a desirable particle size (∼106 nm) and exhibited a spherical morphology, as confirmed by scanning electron and atomic force microscopy. In vitro studies conducted on B16F10 cell lines demonstrated higher cytotoxicity of Exo-HES compared to free HES, supported by enhanced cellular uptake validated through coumarin-6-loaded exosomes. This superior cytotoxicity was further evidenced by DNA fragmentation, increased generation of free radicals (ROS), loss of mitochondrial membrane potential, and effective inhibition of colony formation. The antimetastatic properties of Exo-HES were confirmed through wound healing and transwell migration assays. Oral pharmacokinetics studies revealed a remarkable increase of approximately 2.5 times in oral bioavailability and half-life of HES when loaded into exosomes. Subsequent in vivo experiments utilizing a B16F10-induced melanoma model in Swiss mice established that Exo-HES exhibited superior anticancer activity compared to HES after oral administration. Importantly, no biochemical, hematological, or histological toxicities were observed in tumor-bearing mice treated with Exo-HES. These findings suggest that exosomes loaded with HES represent a promising nanocarrier strategy to enhance the therapeutic effectiveness of hesperidin in melanoma treatment.

Development and comparison of machine learning models for in-vitro drug permeation prediction from microneedle patch.

The field of machine learning (ML) is advancing to a larger extent and finding its applications across numerous fields. ML has the potential to optimize the development process of microneedle patch by predicting the drug release pattern prior to its fabrication and production. The early predictions could not only assist the in-vitro and in-vivo experimentation of drug release but also conserve materials, reduce cost, and save time. In this work, we have used a dataset gleaned from the literature to train and evaluate different ML models, such as stacking regressor, artificial neural network (ANN) model, and voting regressor model. In this study, models were developed to improve prediction accuracy of the in-vitro drug release amount from the hydrogel-type microneedle patch and the in-vitro drug permeation amount through the micropores created by solid microneedles on the skin. We compared the performance of these models using various metrics, including R-squared score (R2 score), root mean squared error (RMSE), and mean absolute error (MAE). Voting regressor model performed better with drug permeation percentage as an outcome feature having RMSE value of 3.24. In comparison, stacking regressor have a RMSE value of 16.54, and ANN model has shown a RMSE value of 14. The value of permeation amount calculated from the predicted percentage is found to be more accurate with RMSE of 654.94 than direct amount prediction, having a RMSE of 669.69. All our models have performed far better than the previously developed model before this research, which had a RMSE of 4447.23. We then optimized voting regressor model's hyperparameter and cross validated its performance. Furthermore, it was deployed in a webapp using Flask framework, showing a way to develop an application to allow other users to easily predict drug permeation amount from the microneedle patch at a particular time period. This project demonstrates the potential of ML to facilitate the development of microneedle patch and other drug delivery systems.

Comprehensive Analysis of Omicron Subvariants: EG.5 Rise, Vaccination Strategies, and Global Impact.

The emergence of new variants of the SARS-CoV-2 virus during the COVID-19 pandemic has prompted significant developments in the understanding, monitoring, and response to these strains. This comprehensive review focuses on two prominent variants of interest (VoI), XBB. 1.5 (Kraken) and XBB.1.16 ("Arcturus"), along with seven variants under observation (VuM), including EG.5. The World Health Organization (WHO) identified these variants in July 2023, highlighting EG.5's noteworthy rise in prevalence. EG.5, also known as "Eris," has exhibited an increased effective reproductive rate, prompting concerns about its contagiousness and immune evasion capabilities. With an altered spike protein in the Receptor-Binding Domain (RBD), EG.5 shares similarities with XBB.1.5 but surpasses it in prevalence, constituting 20% of COVID-19 cases in the United States by late August. EG.5's subvariant, EG.5.1, poses challenges with mutations like Q52H and F456L, contributing to its ability to bypass neutralizing antibodies. The global distribution of SARS-CoV-2 variants presents a dynamic landscape, with XBB.1.16 and other strains gaining prominence. The advent of the BA.2.86 variant further complicates the scenario, with its notable spread in regions lacking robust viral surveillance. A thorough analysis of mutations reveals the evolving nature of the Omicron variant, with distinct amino acid changes characterizing XBB.1.5, XBB.1.16, and EG.5. The WHO designates EG.5 as a "variant of interest" due to its increased contagiousness and potential immune evasion, emphasizing the need for vigilant monitoring. The risk assessment of EG.5 underscores its rapid development and growing prevalence globally. While booster vaccines targeting XBB.1.5 are in development, antiviral medications like nirmatrelvir/ritonavir (Paxlovid) continue to exhibit efficacy. In the context of the evolving variants, the FDA has granted emergency use authorization for updated COVID-19 vaccines targeting circulating strains, reflecting the adaptability of vaccination strategies to address emerging challenges. This comprehensive overview provides a nuanced understanding of the diverse Omicron subvariants, their global impact, and the ongoing efforts to combat their spread through vaccination and therapeutic interventions.

Novel carbamodithioate regulates cellular hypoxia through chemical activation of prolyl hydroxylase-2 for breast cancer chemoprevention.

Inhibition of prolylhydroxylase-2 (PHD-2) in both normoxic and hypoxic cells is a critical component of solid tumours. The present study aimed to identify small molecules with PHD-2 activation potential. Virtually screening 4342 chemical compounds for structural similarity to R59949 and docking with PHD-2. To find the best drug candidate, hits were assessed for drug likeliness, antihypoxic and antineoplastic potential. The selected drug candidate's PHD-2 activation, cytotoxic and apoptotic potentials were assessed using 2-oxoglutarate, MTT, AO/EtBr and JC-1 staining. The drug candidate was also tested for its in-vivo chemopreventive efficacy against DMBA-induced mammary gland cancer alone and in combination with Tirapazamine (TPZ). Virtual screening and 2-oxoglutarate assay showed BBAP-6 as lead compound. BBAP-6 exhibited cytotoxic and apoptotic activity against ER+ MCF-7. In carmine staining and histology, BBAP-6 alone or in combination with TPZ restored normal surface morphology of the mammary gland after DMBA produced malignant alterations. Immunoblotting revealed that BBAP-6 reduced NF-κB expression, activated PHD-2 and induced intrinsic apoptotic pathway. Serum metabolomics conducted with 1H NMR confirmed that BBAP-6 prevented HIF-1α and NF-κB-induced metabolic changes in DMBA mammary gland cancer model. In a nutshell, it can be concluded that BBAP-6 activates PHD-2 and exhibits anticancer potential.

Assessing the synergistic potential of bacteriophage endolysins and antimicrobial peptides for eradicating bacterial biofilms.

Phage-encoded endolysins have emerged as a potential substitute to conventional antibiotics due to their exceptional benefits including host specificity, rapid host killing, least risk of resistance. In addition to their antibacterial potency and biofilm eradication properties, endolysins are reported to exhibit synergism with other antimicrobial agents. In this study, the synergistic potency of endolysins was dissected with antimicrobial peptides to enhance their therapeutic effectiveness. Recombinantly expressed and purified bacteriophage endolysin [T7 endolysin (T7L); and T4 endolysin (T4L)] proteins have been used to evaluate the broad-spectrum antibacterial efficacy using different bacterial strains. Antibacterial/biofilm eradication studies were performed in combination with different antimicrobial peptides (AMPs) such as colistin, nisin, and polymyxin B (PMB) to assess the endolysin's antimicrobial efficacy and their synergy with AMPs. In combination with T7L, polymyxin B and colistin effectively eradicated the biofilm of Pseudomonas aeruginosa and exhibited a synergistic effect. Further, a combination of T4L and nisin displayed a synergistic effect against Staphylococcus aureus biofilms. In summary, the obtained results endorse the theme of combinational therapy consisting of endolysins and AMPs as an effective remedy against the drug-resistant bacterial biofilms that are a serious concern in healthcare settings.

Cystine-cored diphenylalanine appended peptide-based self-assembled fluorescent nanostructures direct redox-responsive drug delivery.

Fabrication of stimuli-responsive superstructure capable of delivering chemotherapeutics directly to the cancer cell by sparing healthy cells is crucial. Herein, we developed redox-responsive hollow spherical assemblies through self-assembly of disulfide-linked cysteine-diphenylalanine (SN). These fluorescent hollow spheres display intrinsic green fluorescence, are proteolytically stable and biocompatible, and allow for real-time monitoring of their intracellular entry. The disulfide bond facilitates selective degradation in the presence of high glutathione (GSH) concentrations, prevalent in cancer cells. We achieved efficient encapsulation (68.72%) of the anticancer drug doxorubicin (Dox) and demonstrated GSH-dependent, redox-responsive drug release within cancerous cells. SN-Dox exhibited a 20-fold lower effective concentration (2.5 µM) for compromising breast cancer cell viability compared to non-malignant cells (50 µM). The ability of SN-Dox to initiate DNA damage signaling and trigger apoptosis was comparable to that of the unencapsulated drug. Our findings highlight the potential of SN for creating site-specific drug delivery vehicles for sustained therapeutic release.

Site-directed mutagenesis at the Glu78 in Ec-NhaA transporter impacting ion exchange: a biophysical study.

Na+/H+ antiporters facilitate the exchange of Na+ for H+ across the cytoplasmic membrane in prokaryotic and eukaryotic cells. These transporters are crucial to maintain the homeostasis of sodium ions, consequently pH, and volume of the cells. Therefore, sodium/proton antiporters are considered promising therapeutic targets in humans. The Na+/H+ antiporter in Escherichia coli (Ec-NhaA), a prototype of cation-proton antiporter (CPA) family, transports two protons and one sodium (or Li+) in opposite direction. Previous mutagenesis experiments on Ec-NhaA have proposed Asp164, Asp163, and Asp133 amino acids with the significant implication in functional and structural integrity and create site for ion-binding. However, the mechanism and the sites for the binding of the two protons remain unknown and controversial which could be critical for pH regulation. In this study, we have explored the role of Glu78 in the regulation of pH by Ec-NhaA. Although we have created various mutants, E78C has shown a considerable effect on the stoichiometry of NhaA and presented comparable phenotypes. The ITC experiment has shown the binding of ~ 5 protons in response to the transport of one lithium ion. The phenotype analysis on selective medium showed a significant expression compared to WT Ec-NhaA. This represents the importance of Glu78 in transporting the H+ across the membrane where a single mutation with Cys amino acid alters the number of H+ significantly maintaining the activity of the protein.

Characterizing the Conformational Dynamics of Human SUMO2: Insights into its Interaction with Metal Ions and SIMs.

SUMO (Small Ubiquitin-like Modifiers) proteins are involved in a crucial post-translational modification commonly termed as SUMOylation. In this work, we have investigated the native-state conformational flexibility of human SUMO2 and its interaction with Cu2+ and Zn2+ ions using 15N-1H based 2D NMR spectroscopy. After SUMO1, SUMO2 is the most studied SUMO isoform in humans which shares 45 % and ~80 % similarity with SUMO1 in terms of sequence and structure, respectively. In this manuscript, we demonstrate that compared to SUMO1, several amino acids around the α1-helix region of SUMO2 access energetically similar near-native conformations. These conformations could play a crucial role in SUMO2's non-covalent interactions with SUMO interaction motifs (SIMs) on other proteins. The C-terminal of SUMO2 was found to bind strongly with Cu2+ ions resulting in a trimeric structure as observed by gel electrophoresis. This interaction seems to interfere in its non-covalent interaction with a V/I-x-V/I-V/I based SIM in Daxx protein.

Measuring the Effect of Ayushman Bharat-Pradhan Mantri Jan Aarogya Yojna (AB-PMJAY) on Health Expenditure among Poor Admitted in a Tertiary Care Hospital in the Northern State of India.

Background: Ayushman Bharat-Pradhan Mantri Jan Aarogya Yojna (AB-PMJAY) as a financial risk protection scheme intends to reduce catastrophic health expenditure (CHE), especially among poor. The current study was carried out to assess the utility of AB-PMJAY in terms of reduction in CHE from before and after admission in a tertiary hospital in the northern state of India. Methodology: It was a hospital-based cross-sectional study carried out from August 2020 to October 2021 at a public tertiary hospital of Himachal Pradesh, India. Data were collected from surgery- and medicine-allied (SA and MA) specialties. Along with socio-demographic details, information for total monthly family expenditure (TMFE), out-of-pocket expenditure (OOPE), and indirect illness-related expenditure (IIE) was recorded before and after hospital admission. CHE was considered as more than 10.0% OOPE of THFE and more than 40.0% of capacity to pay (CTP). Results: A total of 336 participants with a mean age of 46 years were recruited (MA: 54.6%). The majority (~93.0%) of participants had illness of fewer than 6 months. The mean TMFE was observed to be INR 4213.1 (standard deviation: 2483.7) and found to be similar across specialties. The OOPE share of TMFE declined from 76.1% (before admission) to 30.0% (after admission). Before admission, CHE was found among 65.5% (10.0% of THFE) and 54.2% (40.0% of CTP) participants. It reduced to about 29.0% (based on both THE and CTP) after admission to hospital. Conclusion: AB-PMJAY scheme found to be useful in reducing CHE in a tertiary hospital.

Are We Providing Enough Information to the Pathologists? An Audit of Filling of Histopathology Request Forms for Surgically Resected Tumours.

OBJECTIVE: To analyse quantitatively the adequacy of demographics of clinical information and highlight specific areas of neglect, by assessing the adequacy of filling out histopathology request forms. STUDY DESIGN: Clinical Audit. Place and Duration of the Study: Department of Pathology, Dow University of Health Sciences (DUHS), Karachi, Pakistan, from January to September 2021. METHODOLOGY: A retrospective audit was carried out on the request forms of surgically resected tumours and biopsies. The recorded details of the patients' demographics and biopsy, clinical history and examination, and intraoperative findings were analysed. RESULTS: Out of 175 forms, patients' names were written in 174 (99.4%) while medical record numbers were written in 113 (64.6%). The doctors' names were given in 172 (98.3%) forms and phone numbers in 34 (19.4%). A clinical diagnosis was provided in 164 (93.7%) forms, while 152 (86.9%) forms correctly entered the biopsy site. Sixty-seven (38.3%) forms included the correct nature of the biopsy. Relevant operative details were provided in half of the forms. Symptoms and their duration were mentioned in 144 (82.3%) and 100 (57.1%), respectively. The form-filling rate was the same for both benign and malignant tumours. CONCLUSION: This study shows that in a significant proportion of cases, complete relevant information is not provided to the histopathologists on request forms for logistics. KEY WORDS: Histopathology, Request forms, Tumours, Audit.

Recent advances in toxicological research of di-(2-ethylhexyl)-phthalate: Focus on endoplasmic reticulum stress pathway.

The plasticizer di-(2-ethylhexyl)-phthalate (DEHP) is the most significant phthalate in production, usage, and environmental occurrence. DEHP is found in products such as personal care products, furniture materials, cosmetics, and medical devices. DEHP is noncovalently bind with plastic therefore, repeated uses lead to leaching out of it. Exposure to DEHP plasticizers leads to toxicity in essential organs of the body through various mechanisms. The main objective of this review article is to focus on the DEHP-induced endoplasmic reticulum (ER) stress pathway implicated in the testis, brain, lungs, kidney, heart, liver, and other organs. Not only ER stress, PPAR-related pathways, oxidative stress and inflammation, Ca2+ homeostasis disturbances in mitochondria are also identified as the relative mechanisms. ER is involved in various critical functions of the cell such as Protein synthesis, protein folding, calcium homeostasis, and lipid peroxidation but, DEHP exposure leads to augmentation of misfolded/unfolded protein. This review complies with various recently reported DEHP-induced toxicity studies and some pharmacological interventions that have been shown to be effective through ER stress pathway. DEHP exposure does assess health risks and vulnerability to populations across the globe. This study offers possible targets and approaches for addressing various DEHP-induced toxicity.

A Rare Case of Postpartum Paraplegia: A Case Report.

In this case report, a 27-year-old woman who had pre-eclampsia in the past and had a cesarean section as a result of the condition presents with an uncommon and difficult form of postpartum paraplegia. She experienced bilateral lower limb paralysis and urine incontinence soon after the surgery, which quickly led to unconsciousness and required mechanical ventilator support and intensive care treatment. Comprehensive diagnostic testing, which included magnetic resonance imaging scans of the brain and spinal cord, identified signs typical of "Posterior Reversible Encephalopathy Syndrome (PRES)" and spinal cord infarction affecting segments C3 to D2. "Antiphospholipid Antibody Syndrome (APLA)" was identified by laboratory testing, highlighting the significance of taking a thorough approach to comprehending this uncommon clinical condition. Treatment included anticoagulant therapy, high-dose steroid therapy, and antihypertensive drugs, emphasizing the crucial importance of inter-disciplinary care in handling such complex situations. Even if the patient's symptoms have partially improved, their condition is still being closely monitored in the intensive care unit. In the context of postpartum neurological problems and the complex interplay between pre-eclampsia, spinal cord infarction, and related clinical symptoms, this case emphasizes the need for increased awareness and prompt management.