Diagnosis of the Initial Stage of Hepatocellular Carcinoma: A Review.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. There may be more than a million instances of hepatocellular carcinoma by 2025, making it a persistent concern for global health. The most common form of hepatocellular carcinoma accounts for more than 90% of cases. There is no known cure for hepatocellular carcinoma, which is usually detected late in life. Unlike most other common malignancies, such as lung, prostate, and breast cancers, where mortality rates are declining, rates of death are rising by around 2-3% every year. It is extremely difficult to diagnose hepatocellular carcinoma in its early stages. Alpha-fetoprotein serology studies and ultrasonography (US) monitoring were historically the primary methods for early detection of hepatocellular cancer. However, the sensitivity or specificity of ultrasonography/alpha-fetoprotein (US/AFP) is not high enough to detect hepatocellular carcinoma in its early stages. Alpha-fetoprotein, or AFP, is an amino acid that is normally produced by the liver or yolk sac of an embryonic baby. In adults, AFP levels are typically modest. Adults with high levels of AFP have been associated with several illnesses, the most well-known of which are certain types of cancer. It is still possible to diagnose hepatocellular carcinoma early because of current technological advancements. We address the advancements in the diagnosis of hepatocellular carcinoma in this article, with a focus on new imaging techniques and diagnostic markers for early-stage tumor identification.

Sulphonated poly(ethersulfone)/carbon nano-onions-based nanocomposite membranes with high ion-conducting channels for salt removal via electrodialysis.

Herein, we are reporting the carbon nano onions (CNO)-based sulphonated poly(ethersulfone) (SPES) composite membranes by varying CNO content in SPES matrix for water desalination applications. CNOs were cost-effectively synthesized using flaxseed oil as a carbon source in an energy efficient flame pyrolysis process. The physico- and electrochemical properties of nanocomposite membranes were evaluated and compared to pristine SPES. Moreover, the chemical characterisation of composite membranes and CNOs were illustrated using techniques such as nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscope (FE-SEM), thermogravimetric analysis (TGA) and universal tensile machine (UTM). In the series of nanocomposite membranes, SPES-0.25 composite membrane displayed the highest water uptake (WU), ion exchange membrane (IEC) and ionic conductivity (IC) values that were enhanced by 9.25%, ~ 44.78% and ~ 6.10%, respectively, compared to pristine SPES membrane. The electrodialytic performance can be achieved maximum when membranes possess low power consumption (PC) and high energy efficiency (Ee). Therefore, the value of Ee and Pc for SPES-0.25 membrane has been determined to be 99.01 ± 0.97% and 0.92 ± 0.01 kWh kg-1, which are 1.12 and 1.11 times higher than the pristine SPES membrane. Hence, integrating CNO nanoparticles into the SPES matrix enhanced the ion-conducting channels.

Tumors Involving the Infratemporal Fossa: A Systematic Review of Clinical Characteristics and Treatment Outcomes.

BACKGROUND: Infratemporal fossa (ITF) tumors represent various pathologies and are seldom described in the literature, reflecting their rarity. Here we review the literature on tumors invading ITF and describe patient characteristics, treatment strategies, and clinical outcomes. METHODS: Relevant articles were retrieved from PubMed, Scopus, and Cochrane. A systematic review and meta-analysis were conducted on the clinical presentation, treatment protocols, and clinical outcomes. RESULT: A total of 27 articles containing 106 patients with ITF tumors (median tumor size: 24.3 cm3 [interquartile range, 15.2-42 cm3]) were included (median age: 46 years [interquartile range, 32-55 years]; 59.4% were males]). Of the confirmed tumor pathology data, schwannomas (n = 24; 26.1%) and meningiomas (n = 13; 14.1%) were the most common tumors. Facial hypoesthesia (n = 22; 18.5%), auricular/preauricular pain (n = 20; 16.8%), and headaches (n = 11; 9.2%) were the most common presenting symptoms. Of patients who had surgical resection (n = 97; 95.1%), 70 (73.7%) had transcranial surgery (TCS) and 25 (26.3%) had endoscopic endonasal surgery (EES). Among available details on the extent of resection (n = 84), gross-total resection (GTR) was achieved in 62 (73.8%), and 5 (6.0%) had biopsy only. Thirty-five (33.0%) patients had postoperative complications. Among cases with available data on reconstruction techniques (n = 8), four (50%) had adipofascial antero-lateral thigh flap, three (37.5%) had latissimus dorsi free flap, and one (12.5%) had antero-lateral thigh flap. Fourteen (13.2%) patients had adjuvant chemotherapy, and sixteen (15.1%) had adjuvant radiotherapy. During a median follow-up time of 28 months (IQR, 12.25-45.75 months), 15 (14.2%) patients had recurrences, and 18 (17.0%) patients died. The median overall survival (OS) time was 36 months (95% confidence interval: 29-41 months), and the 5-year progression-free survival (PFS) rate was 61%. CONCLUSION: Various tumor types with different biological characteristics invade the ITF. The present study describes patient demographics, clinical presentation, management, and outcomes. Depending on the tumor type and patient condition, patient-tailored management is recommended to optimize treatment outcomes.

Hydrophobically Modified Abelmoschus esculentus Polysaccharide Based Nanoparticles and Applications: A Review.

Nanomaterials are indeed a nanoscale technology that deals with the creation, evaluation, fabrication, and utilization of systems at the nanometre scale by manipulating their size and shape. We consider natural polysaccharides such as promising polysaccharides, which are biodegradable, nontoxic, abundant, and inexpensive bio-polymeric precursors for preparing the materials of choice in various industries. The aim is to review different methods to produce hydrophobically modified Abelmoschus esculentus nanoparticles and study the evaluation processes of these nanoparticles as given in the literature. It proved the benefits of derivatives of gum by introducing different chemical groups. The chemical functionalization of gum mainly includes the esterification, etherification, and crosslinking reactions of the hydroxyl groups and contains a special fibre which takes sugar levels in the blood under control, providing a sugar quantity suitable for the bowels. Okra contains mucilage that helps remove poisonous chemicals and bad cholesterol, often overloads the liver. Recovering from psychological conditions, like depression, general weakness, and joint healthiness can be done with Okra. Someone additionally applied it for pulmonary inflammation, bowel irritation, and sore throat. Purgative properties okra possesses are beneficial for bowel purification. It is used to counteract the acids. Fibre okra contains a valuable nutrient for intestinal microorganisms and ensures proper intestine functionality. It also protects the mucosa of the digestive tract by covering them with an extra layer because of its alkaline nature. Nanotechnology has emerged as a critical component of pharmaceutics, with many applications in drug carriers of interest aimed at improving drug clinical outcomes such as cancer, diabetes mellitus, wound care management, atopic dermatitis, cosmeceutical, etc. Beneficial outcomes of this review are discussed briefly.

Vesicular Approach Review on Nanocarriers bearing Curcumin and Applications.

Phytoconstituents have been used to treat a variety of human diseases for a long time, but their use in pharmaceuticals is limited because of their low aqueous solubility. Researchers have created vesicular systems to address many of the issues associated with the bioavailability and therapeutic efficacy of poorly water-soluble drugs and target the drug to the desired location in the body. Several vesicular nanocarrier systems have been developed. Review contrasts various vesicular drug delivery systems, including liposomes, sphingosomes, emulsomes, niosomes, ethosomes, virosomes, phytosomes, aquasomes, proniosomes, transfersomes, pharmacosomes. Vesicular drug delivery systems have caused a scientific revolution, which has resulted in the development of novel dosage forms. This review aims to illustrate the applications, advantages, and disadvantages of the vesicular approach as nanocarriers bearing curcumin and widely used in gene delivery, tumor-targeting to the brain, oral formulations, and resolving various problems associated with drug stability and permeability issues. Nanocarriers also has wide application as green nanocomposites and for antitubercular drugs depending on their physical properties.

People living with mental disorder in Nigeria amidst COVID-19: Challenges, implications, and recommendations.

COVID-19 has become a global public health obstacle. This disease has caused negligence on mental health institutions, decreased trust in the healthcare system and traditional and religious beliefs, and has created a widespread stigma on people living with mental health illness, specifically in Nigeria. The increase of COVID-19 cases that have exhausted the healthcare system in Nigeria have brought further negligence to people living with mental disorder, thus increasing the burden of the disease on these patients. Overall, this article considerably highlighted the need for equal accessibility to healthcare resources, as well as the requirement of proper attention and care for mental health patients in Nigeria. This article discusses the challenges that surfaced because of the COVID-19 pandemic on people living with mental illness and their implications, as well as suggesting necessary actions and recommendations.

Advances in chemistry and composition of soft materials for drug releasing contact lenses.

Ocular drug delivery has always been a challenging feat to achieve in the field of medical sciences. One of the existing methods of non-invasive ocular drug delivery is the use of eye drops. However, drugs administered through these formulations have low bioavailability in the ocular system. This limitation can been overcome by using contact lenses as drug delivery vehicles. According to USA FDA definitions they can be categorized into two main categories-hard and soft contact lenses. Based on the material properties, hard contact lenses are mostly produced from polymers of acrylate monomers such as MMA (methyl methacrylate). These have the least water retention capacity, thereby, having minimal ability to diffuse oxygen into the corneal layer and are not ideal for long term use. Soft material contact lenses are flexible and are mainly hydrogel based. They have higher water retention capacities as compared to rigid contact lenses, which gives them the ability to transmit oxygen to the corneal layer. These hydrogel based soft materials are mainly produced from polymers of acrylate monomers such as HEMA (hydroxyethyl methacrylate) and found to be better for drug delivery contact lenses. These polymer-based soft materials have been efficiently modified in terms of their chemistry to achieve diverse physicochemical properties to produce efficient ocular drug delivery systems. However, complications such as drug leaching during storage and distribution, sterilisation, preservation of integrity of the lens and the possibility of surface roughness due to the incorporated drug molecules still need to be optimised. This review highlights the chemistries of various polymeric molecules through which physicochemical properties can be modified to achieve optimum drug loading and sustained release of the drug for application in the ocular system.

Whole Genome Sequencing of Mycobacterium tuberculosis Clinical Isolates From India Reveals Genetic Heterogeneity and Region-Specific Variations That Might Affect Drug Susceptibility.

Whole genome sequencing (WGS) of Mycobacterium tuberculosis has been constructive in understanding its evolution, genetic diversity and the mechanisms involved in drug resistance. A large number of sequencing efforts from across the globe have revealed genetic diversity among clinical isolates and the genetic determinants for their resistance to anti-tubercular drugs. Considering the high TB burden in India, the availability of WGS studies is limited. Here we present, WGS results of 200 clinical isolates of M. tuberculosis from North India which are categorized as sensitive to first-line drugs, mono-resistant, multi-drug resistant and pre-extensively drug resistant isolates. WGS revealed that 20% of the isolates were co-infected with M. tuberculosis and non-tuberculous mycobacteria species. We identified 12,802 novel genetic variations in M. tuberculosis isolates including 343 novel SNVs in 38 genes which are known to be associated with drug resistance and are not currently used in the diagnostic kits for detection of drug resistant TB. We also identified M. tuberculosis lineage 3 to be predominant in the northern region of India. Additionally, several novel SNVs, which may potentially confer drug resistance were found to be enriched in the drug resistant isolates sampled. This study highlights the significance of employing WGS in diagnosis and for monitoring further development of MDR-TB strains.

Studies on biological macromolecules lipid-Gelucire based gastroretentive multiparticulate.

Studies on biological macromolecules lipid-Gelucire based sustained release gastroretentive multiparticulates of metformin hydrochloride (MH) were developed by dispersing MH in melted Gelucire 39/01 and 43/01 using the melt granulation technique while fast release solid dispersions gastroretentive multiparticulates of glibenclamide (GLB), poorly soluble drug were developed using Gelucire 50/13 and PEG 200, 400, 4000, 6000 as carrier at different ratios. Percent drug entrapment of MH was 99.6±0.35% and in vitro floating ability was 11.3±0.47h. Model dependent analysis shows that zero order kinetics was followed while drug release mechanism was anomalous diffusion controlled. Combination of ethylcellulose, methylcellulose and microcrystalline cellulose with Gelucire were explored for release of drug, floatability and consistency for optimized formulation. While GLB multiparticulates showed entrapment efficiency of 99.8±0.11%, in vitro buoyancy for 11±0.2h and improved solubility and dissolution rate. Zero order kinetics was promising for all formulations. Model independent analysis f2 value for GIV was 40 while for M II was 54. Characterization was done by SEM, FTIR and PXRD. RP-HPLC method was adopted for simultaneous pharmacokinetic analysis of the drugs in rat plasma. In IVIVC studies confirm increased bioavailability of drugs in combination form and followed level A correlation using the diabetic type II Wistar rat.

Determination of drug susceptibility patterns and genotypes of Mycobacterium tuberculosis isolates from Kanpur district, North India.

BACKGROUND AND OBJECTIVES: Molecular typing of Mycobacterium tuberculosis isolates has greatly facilitated the understanding of tuberculosis epidemiology. This study was done to characterize prevalent M. tuberculosis genotypes in a defined area of Kanpur district, North India by spoligotyping and IS6110-Restriction Fragment Length Polymorphism (RFLP) and to correlate the genotypes identified with their drug susceptibility patterns. METHODS: Ninety-eight patients had clinical features suggestive of pulmonary tuberculosis (PTB) and out of them, 22 were new smear positive PTB (CAT I DOTS), 48 smear positive re-treatment, defaulters and CAT I failure PTB (CAT II DOTS) and 28 new smear negative PTB (CAT III). Out of them, sputum culture was positive for M. tuberculosis in 74 cases. DNA was extracted from growth on Lowenstein-Jensen slants and subjected to spoligotyping. Clusters were subsequently analyzed with IS6110 RFLP. Drug susceptibility testing was done for rifampicin, isoniazid, ethambutol, ofloxacin, streptomycin and kanamycin. RESULTS: Thirty-seven spoligo patterns were observed. Predominant spoligotypes belonged to Central Asian Delhi family (33.78%), Beijing family (10.8%), East African-Indian family (5.4%), T1 family (5.4%) and U family (4.1%). RFLP analysis revealed 66% isolates had more than 10 IS6110 copies while 17% isolates each had low (1-5) and intermediate (6-9) copy numbers. All the isolates clustered by spoligotyping were identified unique by RFLP. Resistance to at least one drug was present in 35 (47.3%), out of which 8 patients belonged to CAT I and 27 to CAT II. Eleven (14.86%) were multi drug-resistant (MDR) and out of them, 6 (54.5%) isolates were of ST1/Beijing family. MDR-TB was significantly higher in Beijing strain than others (p<0.0001), however, most (83%) were from previously treated cases and thus can not be linked with recent transmission. CONCLUSION: This approach of molecular typing appears promising and merits further evaluation to study dynamics of TB transmission specially in India.

In vitro effect of fluoroquinolones against Mycobacterium tuberculosis isolates from Agra & Kanpur region of north India.

BACKGROUND & OBJECTIVE: Fluoroquinolones (FQs) are important drugs used for treatment of drug resistant tuberculosis and are also now being considered as first line drugs to shorten the duration of treatment of tuberculosis (TB). In order to find out useful FQs for treatment of tuberculosis, the comparative efficacy of five FQs, namely, ofloxacin (OFL), ciprofloxacin (CIP), sparfloxacin (SPX), gatifloxacin (GAT) and levofloxacin (LEVX) was studied against Mycobacterium tuberculosis (MTB) isolates obtained from both treated and untreated patients from Agra and Kanpur regions of north India. METHODS: A total of 162 MTB isolates [including 110 MTB isolates obtained from untreated patients (Cat-I) and 52 isolates from treated patients (Cat-II)] were tested for their susceptibilities to FQs using standard minimum inhibitory concentration (MIC) method on Löwenstein-Jensen medium. RESULTS: Keeping in view the therapeutically achievable drug levels, it was found that in Cat-I 97.2 per cent (107/110) isolates were sensitive to GAT, 89 per cent (98/110) to LEVX at 1 microg/ml whereas 92.7 per cent (102/110) isolates were inhibited by OFL at 2 microg/ml and 73.6 per cent (81/110) to SPX at 0.5 microg/ml. Only 63.6 per cent (70/110) isolates were found to be sensitive to CIP at 2 microg/ml which increased to 89 per cent (98/110) at 4 microg/ml (higher than achievable peak serum level). On the other hand, among 52 isolates for Cat-II, 37 (71.2%) were found to be sensitive to GAT and 33 (63.5%) to LEVX at 1 microg/ml concentration, 28 (53.8%) to SPX at 0.5 microg/ml whereas 33 (63.5%) and 24 (46.2%) isolates were found to be sensitive to OFL and CIP at 2 microg/ml, respectively. INTERPRETATION & CONCLUSION: It appears that GAT has higher activity against MTB isolates followed by OFL, LEVX and SPX whereas CIP showed the lowest activity. GAT was also found to be the most effective FQ against multi-drug resistant (MDR) isolates both from Cat-I and Cat-II patients. Thus, except CIP, other FQs showed potential to be included in the treatment regimens of tuberculosis including MDR-TB.

Role of embCAB gene mutations in ethambutol resistance in Mycobacterium tuberculosis isolates from India.

In the present study, ethambutol (EMB) resistance-associated mutations were characterised in the embCAB genes of clinical isolates of Mycobacterium tuberculosis (MTB) collected in India. Thirty MTB isolates were tested for their susceptibility to first-line antitubercular drugs using the Löwenstein-Jensen proportion method, and EMB minimum inhibitory concentrations of MTB isolates were determined by the resazurin microtitre assay. Sequencing of various regions of the embCAB genes was performed to identify EMB resistance-associated mutations. Mutations of embB306 were detected in 15 of 23 EMB-resistant MTB isolates. Three EMB-resistant isolates had mutations at codon 270 of the embC gene, two of which also harboured embB306 mutations. No mutation was identified in the embA gene. All seven EMB-sensitive MTB isolates had the wild-type embCAB sequence. In summary, embB306 mutations were associated with EMB resistance, and mutation at codon 270 of the embC gene may contribute to high-level EMB resistance in some MTB isolates.

Molecular typing of Mycobacterium tuberculosis isolates from a rural area of Kanpur by spoligotyping and mycobacterial interspersed repetitive units (MIRUs) typing.

Molecular typing of Mycobacterium tuberculosis isolates has greatly facilitated the understanding of epidemiology of tuberculosis (TB). This study was done to characterize prevalent genotypes of M. tuberculosis on a collection of 97 isolates based on spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing in rural area of Kanpur, North India. In this area different types of interventions are being undertaken and follow-up studies are progressing. Predominant spoligotypes prevalent in this region belonged to Central Asian-Delhi family (CAS1_Del) (37%), East African-Indian family (11%), T1 family (8%) and Beijing (4%) family. Highly distinct MIRU-VNTR genotypes were obtained. Significant spoligotypes such as Beijing and CAS1_Del type were further divided into subtypes with MIRU-VNTR. This preliminary study reveals that CAS is the most predominant family in this rural area of Kanpur. If confirmed in other areas, this combined approach of molecular typing can be preferably be used as first line tool for studying linkage and transmission dynamics of TB in India.

Determination of ethambutol MICs for Mycobacterium tuberculosis and Mycobacterium avium isolates by resazurin microtitre assay.

OBJECTIVES: To test susceptibilities of Mycobacterium tuberculosis (MTB) isolates to ethambutol by the Löwenstein-Jensen (LJ) proportion method and resazurin microtitre assay (REMA) and to evaluate REMA for the determination of ethambutol MICs for MTB and Mycobacterium avium isolates. METHODS: A total of 50 MTB and 20 M. avium isolates were tested to determine the MICs of ethambutol by REMA and agar dilution method. MTB isolates were also tested by the LJ proportion method. RESULTS: REMA provided ethambutol susceptibility results for all the isolates within 8-9 days. For MTB isolates, REMA showed 96.7% sensitivity, 100.0% specificity and 98.0% accuracy when LJ proportion results were taken as 'gold standard'. For both MTB and M. avium isolates, the MICs determined by REMA were lower than those determined in agar medium, indicating that MIC values determined by REMA are closer to the actual MICs for the isolates. CONCLUSIONS: REMA can be used as a rapid and inexpensive method for mycobacterial drug susceptibility testing against ethambutol. In comparison with the agar method, the MICs determined by REMA can more accurately be correlated with achievable plasma concentrations of antimycobacterial agents.