Organogels: "GelVolution" in Topical Drug Delivery - Present and Beyond.

Topical drug delivery holds immense significance in dermatological treatments due to its non-invasive nature and direct application to the target site. Organogels, a promising class of topical drug delivery systems, have acquired substantial attention for enhancing drug delivery efficiency. This review article aims to explore the advantages of organogels, including enhanced drug solubility, controlled release, improved skin penetration, non-greasy formulations, and ease of application. The mechanism of organogel permeation into the skin is discussed, along with formulation strategies, which encompass the selection of gelling agents, cogelling agents, and additives while considering the influence of temperature and pH on gel formation. Various types of organogelators and organogels and their properties, such as viscoelasticity, non-birefringence, thermal stability, and optical clarity, are presented. Moreover, the biomedical applications of organogels in targeting skin cancer, anti-inflammatory drug delivery, and antifungal drug delivery are discussed. Characterization parameters, biocompatibility, safety considerations, and future directions in optimizing skin permeation, ensuring long-term stability, addressing regulatory challenges, and exploring potential combination therapies are thoroughly examined. Overall, this review highlights the immense potential of organogels in redefining topical drug delivery and their significant impact on the field of dermatological treatments, thus paving the way for exciting prospects in the domain.

Nano-Innovations in Cancer Therapy: The Unparalleled Potential of MXene Conjugates.

MXenes are two-dimensional transition metal carbides, nitrides, and carbonitrides that have become important materials in nanotechnology because of their remarkable mechanical, electrical, and thermal characteristics. This review emphasizes how crucial MXene conjugates are for several biomedical applications, especially in the field of cancer. These two-dimensional (2D) nanoconjugates with photothermal, chemotherapeutic, and photodynamic activities have demonstrated promise for highly effective and noninvasive anticancer therapy. MXene conjugates, with their distinctive optical capabilities, have been employed for bioimaging and biosensing, and their excellent light-to-heat conversion efficiency makes them perfect biocompatible and notably proficient nanoscale agents for photothermal applications. The synthesis and characterization of MXenes provide a framework for an in-depth understanding of various fabrication techniques and their importance in the customized formation of MXene conjugates. The following sections explore MXene-based conjugates for nanotheranostics and demonstrate their enormous potential for biomedical applications. Nanoconjugates, such as polymers, metals, graphene, hydrogels, biomimetics, quantum dots, and radio conjugates, exhibit unique properties that can be used for various therapeutic and diagnostic applications in the field of cancer nanotheranostics. An additional layer of understanding into the safety concerns of MXene nanoconjugates is provided by detailing their toxicity viewpoints. Furthermore, the review concludes by addressing the opportunities and challenges in the clinical translation of MXene-based nanoconjugates, emphasizing their potential in real-world medical practices.

Race as a determinant of prenatal depressive symptoms: analysis of data from the 'All Our Families' study.

OBJECTIVES: Prenatal depression is a serious maternal-child health concern. Risk factors and health consequences appear more prevalent in Indigenous communities and ethnic minority groups; however, research on these populations is limited. We examined the following questions: (A) How do pregnant Indigenous women, ethnic minority women, and White women compare on levels of depressive symptoms and possible clinical depression, and on major risk and protective factors? (B) Is non-dominant (non-White) race associated with higher depressive symptoms and possible clinical depression? (C) What factors mediate and moderate the relationship between race and depression? DESIGN: Data were from the All Our Families study (n = 3354 pregnant women from Alberta, Canada). Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS). Descriptive statistics and multivariable regression methods were used to assess the hypotheses that Indigenous and ethnic minority women would have significantly higher mean EPDS score estimates and higher proportions scoring above cut-offs for possible clinical depression, relative to White women. The association between race and depressive symptoms was hypothesised to be partially mediated by risk factors of socioeconomics, health background, discrimination, domestic violence, and psychosocial stress. Potential confounders were age, marital status, and parity. Diet and social support were hypothesised as protective buffers between stress and depressive symptoms. RESULTS: A higher proportion of White women were married, had family income over $80,000, were employed, and had adequate social support, relative to other women. They had significantly lower mean depressive symptom score, and a smaller proportion scored above cut-offs for possible clinical depression. The positive association between race and depressive symptoms appeared to be partially mediated by socioeconomic factors and psychosocial stress. Social support appeared to moderate the association between stress and depressive symptoms. CONCLUSIONS: Strategies to address socioeconomic status, stress, and social support among racialized minority women may reduce the risk for prenatal depression.

Induction of labor versus expectant management in patients with idiopathic polyhydramnios.

OBJECTIVE: To evaluate whether induction of labor is associated with lower risk of cesarean section compared to expectant management in patients with isolated polyhydramnios. STUDY DESIGN: This is a single-center, retrospective cohort study of patients with pregnancies complicated by idiopathic polyhydramnios, documented between 34 and 38 weeks gestation, who were delivered between July 2012 and February 2020. The primary outcome was cesarean delivery. Secondary outcomes included chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, and composite neonatal morbidity. RESULTS: There were 194 patients included with idiopathic polyhydramnios - 115 underwent induction and 79 patients were expectantly managed. Planned induction was associated with a lower rate of CD compared with expectant management but did not meet statistical significance (19.1 % vs 30.4 %, aOR 0.51, 95 % CI 0.24, 1.05). A similar effect was seen when stratifying for parity: both nulliparous (9.1 % vs 16.3 %, aOR 0.59, 95 % CI 0.17, 1.98) and multiparous (32.7 % vs 47.2 %, aOR 0.45, 95 % CI 0.18, 1.15) patients had a lower CD rate when there was a planned induction, though neither group met statistical significance. No differences in maternal or fetal secondary outcomes were identified (chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, composite neonatal morbidity). CONCLUSION: Lower rates of cesarean section were associated with labor induction for patients with isolated polyhydramnios, but confidence intervals did not reach statistical significance.

Ameliorative anticancer effect of dendrimeric peptide modified liposomes of letrozole: In vitro and in vivo performance evaluations.

Letrozole (LTZ) loaded dendrimeric nano-liposomes were prepared for targeted delivery to breast cancer cells. Surface modification with cationic peptide dendrimers (PDs) and a cancer specific ligand, transferrin (Tf), was attempted. Arginine-terminated PD (D-1) and Arginine-terminated, lipidated PD (D-2) were synthesized using Solid Phase Peptide Synthesis, purified by preparative HPLC and characterized using 1HNMR, MS and DSC analyses. Surface modification of drug loaded liposomes with Tf and/or PD was carried out. Formulations were characterized using FTIR, DSC, 1HNMR, XRD and TEM. Tf-conjugated LTZ liposomes (LTf) and Tf/D-2-conjugated LTZ liposomes (LTfD-2) showed greater cytotoxic potential (IC50 = 95.03 µg/mL and 23.75 µg/mL respectively) with enhanced cellular uptake in MCF7 cells compared to plain LTZ. Blocking studies of Tf (Tf-receptor mediated internalization) revealed decreased uptake of LTf and LTfD-2 confirming the role of Tf in uptake of Tf-conjugated liposomes. Intravenous treatment with LTfD-2 caused highest reduction in tumor volumes of female BALB/c-nude mice (145 mm3) compared to plain LTZ (605 mm3) and unconjugated LTZ liposomes (LP) (300 mm3). In vivo biodistribution studies revealed higher fluorescence in tumor tissue and liver of LTfD-2 treated mice than LTf or LP treatment. Immunohistochemical studies revealed greater apoptotic potential of LTfD-2 as indicated by TUNEL assay and ROS detection assay. The study reveals the superior therapeutic efficacy of the developed LTZ liposomal nanocarriers using PDs to enhance the transfection efficiency in addition to modifying the surface characteristics by attaching a targeting ligand for active drug targeting to breast cancer cells.

Promising practices for the design and implementation of sexuality education programmes for youth in India: a scoping review.

Sexual violence and HIV/AIDS are major public health concerns in India. By promoting bodily autonomy, wellbeing, and dignity through knowledge and skills, comprehensive sexuality education for young people can help prevent adverse sexual and reproductive health outcomes. While there is increased recognition globally regarding young people's need for sexuality education, translating this recognition into accepted programmes in India has been challenging. This scoping review aims to examine recommendations for promising practices for the design and implementation of sexuality education programmes and resources aimed at youth in India. A systematic search and review of the literature was conducted from June to August 2020. Of the total 5312 citations identified and screened, 622 advanced to full-text screening, and 39 were included in the final analysis. Promising practices include the need to: tailor content to serve the needs of the specific youth population being targeted; use engaging and participatory methods to teach sexual health content; work in partnership and collaboration with local experts and organisations; address potential barriers to participation and work to mitigate those barriers for marginalised youth; be youth friendly, flexible and convenient; and to be developmentally and culturally appropriate for the Indian youth context. Sexuality education programmes should integrate into existing community services and link with local reproductive health services to help provide youth with access to the services they may need. Continued work and efforts are required to address the interrelated and broad structural factors, including political, financial, social, and cultural factors that affect youth sexual health and wellbeing.

A strategy for evaluation of isotopic enrichment and structural integrity of deuterium labelled compounds by using HR-MS and NMR.

Determining the purity of deuterium labelled compounds is important due to the increasing use of these compounds in mass spectrometry (MS) based quantitative analyses for targeting metabolic flux, reducing toxicity, confirming reaction mechanisms during synthesis, predicting enzyme mechanisms, and enhancing the efficacy of drugs, in quantitative proteomics, and also as internal standards. In the present study, a strategy using liquid chromatography electrospray ionization high resolution mass spectrometry (LC-ESI-HR-MS) and nuclear magnetic resonance (NMR) spectroscopy was proposed to determine the isotopic enrichment and structural integrity of deuterium labelled compounds. The proposed strategy involves recording full scan MS, extracting and integrating isotopic ions, and calculating the isotopic enrichment of the desired labelled compounds. NMR analysis confirms structural integrity or positions of labelled atoms and can provide insights into the relative percent isotopic purity. This strategy was used to evaluate the isotopic enrichment and structural integrity of in-house synthesized compounds as well as a series of commercially available deuterium labelled compounds. The % isotopic purity for labelled compounds of a benzofuranone derivative (BEN-d2), tamsulosin-d4 (TAM-d4), oxybutynin-d5 (OXY-d5), eplerenone-d3 (EPL-d3), and propafenone-d7 (PRO-d7) was calculated and found to be 94.7, 99.5, 98.8, 99.9, and 96.5, respectively. All the samples were run in triplicate and the results were observed to be reproducible.

Isolation and characterization of pseudo degradation products of acalabrutinib using ESI-HRMS/MS and NMR: Formation of possible geometrical isomers.

A forced degradation study of acalabrutinib (ACB), used to treat relapsed mantle cell lymphoma, was performed to identify and characterize all possible major degradation products formed under different stress conditions. The degradation products (DP) were separated using reverse phase UHPLC system on Kinetex EVO C18 column. Major DPs formed were isolated using semi-preparative HPLC and characterized by LC-ESI-HRMS/MS and NMR. ACB degraded to form seven major degradants (DP-I to DP-VII). DP-I and DP-V were formed under alkaline stress condition, whereas DP-II, DP-III, DP-VI and DP-VII were formed under both acidic and basic conditions. Further, DP-IV was formed when ACB drug was exposed to hydrogen peroxide stress condition. ACB was found to be stable when subjected to aqueous (neutral pH), thermal and UV radiation of 254 nm, as it has not shown any significant degradation under these conditions. Interestingly, two pairs of pseudo geometrical isomeric DPs (DP-II and DP-III, DP-VI and DP-VII) were observed. The plausible degradation pathway of ACB and fragmentation patterns of both ACB and major DPs were discussed.

Role of autophagy in tumor response to radiation: Implications for improving radiotherapy.

Autophagy is an evolutionary conserved, lysosome-involved cellular process that facilitates the recycling of damaged macromolecules, cellular structures, and organelles, thereby generating precursors for macromolecular biosynthesis through the salvage pathway. It plays an important role in mediating biological responses toward various stress, including those caused by ionizing radiation at the cellular, tissue, and systemic levels thereby implying an instrumental role in shaping the tumor responses to radiotherapy. While a successful execution of autophagy appears to facilitate cell survival, abortive or interruptions in the completion of autophagy drive cell death in a context-dependent manner. Pre-clinical studies establishing its ubiquitous role in cells and tissues, and the systemic response to focal irradiation of tumors have prompted the initiation of clinical trials using pharmacologic modifiers of autophagy for enhancing the efficacy of radiotherapy. However, the outcome from the Phase I/II trials in many human malignancies has so far been equivocal. Such observations have not only precluded the advancement of these autophagy modifiers in the Phase III trial but have also raised concerns regarding their introduction as an adjuvant to radiotherapy. This warrants a thorough understanding of the biology of the cancer cells, including its spatio-temporal context, as well as its microenvironment all of which might be the crucial factors that determine the success of an autophagy modifier as an anticancer agent. This review captures the current understanding of the interplay between radiation induced autophagy and the biological responses to radiation damage as well as provides insight into the potentials and limitations of targeting autophagy for improving the radiotherapy of tumors.

Income Generation Programs for Persons with Mental Health Challenges: Practices from 13 Indian Mental Health Rehabilitation Centers.

Background: In India, mental health rehabilitation centers run income generation programs (IGP) for therapeutic engagement, skills training, and income generation of clients. The centers have evolved IGP models relevant to their settings. There is a paucity of published literature on practices employed by the centers. Methods: This paper compiles data gathered from visits to 13 centers between November 2018 and April 2019. Information was collected through observation and interviews with staff involved in IGP, using a semi-structured pro forma designed for study. Results: Most centers were based in south India (n = 11) and urban areas (n = 12). Each center ran two to seven IGP. Each center involved 20-50 clients in IGP. Clients involved in IGP were aged 20-60 years. The centers ran a range of IGP, including the manufacturing of household consumables, paper products, textile products, handicraft products, food products, and jute products; animal husbandry and horticulture initiatives; and running cafeterias and petty shops. IGP were mostly selected based on market demand and sales value of products (n = 11); ease of doing (n = 5); interests, abilities, exposure, and experience of clients (n = 5); and availability of resources (n = 3). Products were priced primarily to cover input and labor costs (n = 8), and many centers sold products below the market rates (n = 5). Running stalls during public events was a common strategy for the sale of products (n = 9). Personal contacts and "word of mouth" publicity were used for advertisement (n = 6). Four centers involved family members in IGP. Conclusion: The nature of IGP varied in terms of setting, available resources, and profile of clients availing the services. Marketing and sales were a challenge. A supportive framework of policies and schemes is essential to promote IGP at mental health rehabilitation centers. This report may be helpful for professionals and centers planning to set up an IGP.

Myricetin Allosterically Inhibits the Dengue NS2B-NS3 Protease by Disrupting the Active and Locking the Inactive Conformations.

The dengue NS2B-NS3 protease existing in equilibrium between the active and inactive forms is essential for virus replication, thus representing a key drug target. Here, myricetin, a plant flavonoid, was characterized to noncompetitively inhibit the dengue protease. Further NMR study identified the protease residues perturbed by binding to myricetin, which were utilized to construct the myricetin-protease complexes. Strikingly, in the active form, myricetin binds to a new allosteric site (AS2) far away from the active site pocket and the allosteric site (AS1) for binding curcumin, while in the inactive form, it binds to both AS1 and AS2. To decipher the mechanism for the allosteric inhibition by myricetin, we conducted molecular dynamics simulations on different forms of dengue NS2B-NS3 proteases. Unexpectedly, the binding of myricetin to AS2 is sufficient to disrupt the active conformation by displacing the characteristic NS2B C-terminal ß-hairpin from the active site pocket. By contrast, the binding of myricetin to AS1 and AS2 results in locking the inactive conformation. Therefore, myricetin represents the first small molecule, which allosterically inhibits the dengue protease by both disrupting the active conformation and locking the inactive conformation. The results enforce the notion that a global allosteric network exists in the dengue NS2B-NS3 protease, which is susceptible to allosteric inhibition by small molecules such as myricetin and curcumin. As myricetin has been extensively used as a food additive, it might be directly utilized to fight the dengue infections and as a promising starting material for further design of potent allosteric inhibitors.

Recreation for Psychosocial Rehabilitation of Clients with Mental Health Disorders: A Retropective Review.

Recreation is considered as an important part of rehabilitation as it increases cognitive ability improves social and communication skills among clients with mental health disorders. As part of Psychiatric Rehabilitation Services NIMHANS, weekly recreational activities are conducted for clients with mental health disorders. A retrospective file review of clients' feedback (who participated offline and online) about the recreation session was conducted. Thematic analysis was carried out to analyze the data. Reasons and Benefits of participating in recreation challenges faced, and changes clients would want to bring in the sessions were the themes that emerged. There were differences in the structure of recreation activity conducted in online and offline mode. Overall clients were happy and interested to participate in recreation activities. Recreation should be an integral part of psychosocial rehabilitation for clients with mental health disorders.

Antagonistic Roles of Gallates and Ascorbic Acid in Pyomelanin Biosynthesis of Pseudomonas aeruginosa Biofilms.

Primarily synthesized for chelating metal ions from the surrounding media, the pyomelanin plays an important role in bacterial virulence where it is needed for infection and biofilm formation as well as protection from host immune response. In this study, two out of three phenolic acids, gallic acid, and propyl gallate induced pyomelanin in two clinical isolates of Pseudomonas aeruginosa and inhibited biofilm formation. Ascorbic acid treatment reversed the gallic acid and propyl gallate mediated pyomelanin synthesis without reversing the inhibition of the biofilm formation. mRNA expression study revealed the upregulation of homogentisic acid oxidase enzyme by ascorbic acid treatment, possibly contributing towards the inhibition of pyomelanin synthesis. Tannic acid did not show any antibacterial or pyomelanin-induction activities. The synergistic effect of gallates and ascorbic acid in the inhibition of biofilm formation and associated pyomelanin synthesis was evidenced which needs further studies to establish their antibacterial efficacies, especially against the clinical isolates of Pseudomonas sp.

Delirium and abnormal autonomic nervous system response to head-up tilt testing.

BACKGROUND: Delirium is a common condition with poorly understood pathophysiology. Various theories have been proposed including that delirious patients have reduced cerebral blood flow. We hypothesised that patients with delirium could have abnormal autonomic nervous system function, as assessed by tilt table testing, which would explain the alteration in blood flow. METHODS: A prospective cohort study of medical inpatients aged 65 years and older was undertaken. Delirium was assessed using DRS-R98 and DSM-IV criteria. Beat-to-beat blood pressure (BP) was recorded during tilt testing. Differences in BP changes between the two groups (those with delirium and those without) were explored. The association between severity of delirium and magnitude of BP changes was also examined. RESULTS: 64 participants were recruited during hospitalisation. 29 completed follow-up Head-Up Tilt testing. The mean age of participants was 80.8 years (SD 6.2 years). The control group (n = 12) had a median decrease in systolic BP of 17.5 mmHg (IQR 20.75). The delirium group (n = 17) had a median decrease in systolic BP of 1 mmHg (IQR 38.5), p = 0.04. As delirium severity scores increased, systolic BP change during tilting also increased (rs = 0.42, p = 0.03). CONCLUSION: Participants in the delirium group showed different BP responses to tilt test which may represent abnormal sympathetic response. This would be consistent with other features of delirium such as treatment response to centrally acting alpha-2 blockers. Equity of access to research for older, frail and delirious cohorts is essential but feasibility and acceptability needs to be optimised and factored into study design.

Emerging Roles of PETase and MHETase in the Biodegradation of Plastic Wastes.

Polyethylene terephthalate (PET) is extensively used in plastic products, and its accumulation in the environment has become a global concern. Being a non-degradable pollutant, a tremendous quantity of PET-bearing plastic materials have already accumulated in the environment, posing severe challenges towards the existence of various endangered species and consequently threatening the ecosystem and biodiversity. While conventional recycling and remediation methodologies so far have been ineffective in formulating a "green" degradation protocol, the bioremediation strategies-though nascent-are exhibiting greater promises towards achieving the target. Very recently, a novel bacterial strain called Ideonella sakaiensis 201-F6 has been discovered that produces a couple of unique enzymes, polyethylene terephthalate hydrolase and mono(2-hydroxyethyl) terephthalic acid hydrolase, enabling the bacteria to utilize PET as their sole carbon source. With a detailed understanding of the protein structure of these enzymes, possibilities for their optimization as PET degrading agents have started to emerge. In both proteins, several amino acids have been identified that are not only instrumental for catalysis but also provide avenues for the applications of genetic engineering strategies to improve the catalytic efficiencies of the enzymes. In this review, we focused on such unique structural features of these two enzymes and discussed their potential as molecular tools that can essentially become instrumental towards the development of sustainable bioremediation strategies. Degradation PET by wild type and genetically engineered PETase and MHETase. Effect of the MHETase-PETase chimeric protein and PETase expressed on the surface of yeast cells on PET degradation is also shown.

Facile Synthesis and Characterization of Few-Layer Multifunctional Graphene from Sustainable Precursors by Controlled Pyrolysis, Understanding of the Graphitization Pathway, and Its Potential Application in Polymer Nanocomposites.

The key feature of the present work is the dexterous utilization of an apparently destructive process, pyrolysis, for the synthesis of the most esteemed nanomaterial, graphene. This work is an attempt to synthesize graphene from nonconventional sources such as tannic acid, alginic acid, and green tea by a controlled pyrolysis technique. The precursors used in this work are not petroleum-derived and hence are green. A set of pyrolysis experiments was carried out at different temperatures, followed by a thorough step-by-step analysis of the product morphology, enabling the optimization of the graphitization conditions. A time-dependent morphological analysis was also carried out along with isothermal thermogravimetric studies to optimize the ideal pyrolysis time for graphitization. The specific capacitance of the graphene obtained from alginic acid was 315 F/g, which makes it fairly suitable for application as green supercapacitors. The same graphene was also used to fabricate a rubber-latex-based flexible supercapacitor film with 137 F/g specific capacitance. The graphene and graphene-based latex film exhibited room-temperature magnetic hysteresis, indicating their ferromagnetic nature, which also supports their spintronic applications.

Membrane Depolarization Sensitizes Pseudomonas aeruginosa Against Tannic Acid.

The use of dietary polyphenols as antimicrobial agents has gained immense popularity in recent years, although few of them-like tannic acid has limited use in this field of research; one of the main reasons is its restricted access through the bacterial membrane. Dissipating the bacterial membrane potential with a sub-lethal dosage of the protonophore, carbonyl cyanide m-chlorophenyl hydrazone, enhanced the tannic acid-cytotoxicity with subsequent inhibition of aerobic respiration in Pseudomonas aeruginosa strains which otherwise exhibited a minimum response to tannic acid. However, ascorbic acid, an antioxidant and bacterial membrane-stabilizing compound, had rescued the cells from both tannic acid- and CCCP-mediated lethality. The results suggested that dispersing the membrane potential with a protonophore can enhance the antibacterial properties of tannic acid.