Identification of potent pan-ephrin receptor kinase inhibitors using DNA-encoded chemistry technology.

EPH receptors (EPHs), the largest family of tyrosine kinases, phosphorylate downstream substrates upon binding of ephrin cell surface-associated ligands. In a large cohort of endometriotic lesions from individuals with endometriosis, we found that EPHA2 and EPHA4 expressions are increased in endometriotic lesions relative to normal eutopic endometrium. Because signaling through EPHs is associated with increased cell migration and invasion, we hypothesized that chemical inhibition of EPHA2/4 could have therapeutic value. We screened DNA-encoded chemical libraries (DECL) to rapidly identify EPHA2/4 kinase inhibitors. Hit compound, CDD-2693, exhibited picomolar/nanomolar kinase activity against EPHA2 (Ki: 4.0 nM) and EPHA4 (Ki: 0.81 nM). Kinome profiling revealed that CDD-2693 bound to most EPH family and SRC family kinases. Using NanoBRET target engagement assays, CDD-2693 had nanomolar activity versus EPHA2 (IC50: 461 nM) and EPHA4 (IC50: 40 nM) but was a micromolar inhibitor of SRC, YES, and FGR. Chemical optimization produced CDD-3167, having picomolar biochemical activity toward EPHA2 (Ki: 0.13 nM) and EPHA4 (Ki: 0.38 nM) with excellent cell-based potency EPHA2 (IC50: 8.0 nM) and EPHA4 (IC50: 2.3 nM). Moreover, CDD-3167 maintained superior off-target cellular selectivity. In 12Z endometriotic epithelial cells, CDD-2693 and CDD-3167 significantly decreased EFNA5 (ligand) induced phosphorylation of EPHA2/4, decreased 12Z cell viability, and decreased IL-1ß-mediated expression of prostaglandin synthase 2 (PTGS2). CDD-2693 and CDD-3167 decreased expansion of primary endometrial epithelial organoids from patients with endometriosis and decreased Ewing's sarcoma viability. Thus, using DECL, we identified potent pan-EPH inhibitors that show specificity and activity in cellular models of endometriosis and cancer.

Dual site reactivity of indole-3-Schiff bases with S/Se/Cl substituted ketenes for stereoselective C-4 substituted indole-ß-lactams, biological evaluations, magic chloro effect and molecular docking studies.

A convenient methodology for C-4 indole-ß-lactam hybrids with chloro, sulphur and seleno substitutions through dual site reactivity of indole-3-Schiff bases towards ketenes has been developed. The reaction proceeded in a stereospecific manner with the exclusive formation of trans-ß-lactams assigned with respect to C3-H and C4-H. The synthesized novel ß-lactams have been characterized with the help of elemental analysis (CHNS) and spectroscopic techniques viz.1H NMR, 13C NMR, DEPT 135, HSQC and IR. The trans configuration was further estabilished based on X-ray crystallographic data. Examination of antibacterial properties unveiled that only derivatives 5a and 5b, featuring chloro substitution, exhibited potent activities, underscoring the emergence of the recently coined term "magic chloro effect". Molecular docking analysis provided additional support for the observed in vitro antibacterial activities of compounds 5a-b.

In silico identification of chikungunya virus replication inhibitor validated using biochemical and cell-based approaches.

Discovering an alternative therapy with a long-lasting effect on symptoms caused by chikungunya virus (CHIKV) infection is prompted by the lack of a vaccine and the absence of safe, effective and non-toxic medications. One potential strategy is synthesizing or identifying small compounds that can specifically target the active site of an essential enzyme and prevent virus replication. Previous site-directed mutagenesis studies have demonstrated the crucial role of the macrodomain, which is a part of non-structural protein 3 (nsP3), in virus replication. Exploiting this fact, the macrodomain can be targeted to discover a natural substance that can inhibit its function and thereby impede virus replication. With this aim, the present study focused on potential CHIKV nsP3 macrodomain (nsP3MD ) inhibitors through in silico, in vitro and cell-based methods. Through virtual screening of the natural compound library, nine nsP3MD inhibitors were initially identified. Molecular dynamics (MD) simulations were employed to evaluate these nine compounds based on the stability of their ligand-receptor complexes and energy parameters. Target analysis and ADMET (i.e. absorption, distribution, metabolism, excretion and toxicity) prediction of the selected compounds revealed their drug-like characteristics. Subsequent in vitro investigation allowed us to narrow the selection down to one compound, N-[2-(5-methoxy-1H-indol-3-yl) ethyl]-2-oxo-1,2-dihydroquinoline-4-carboxamide, which exhibited potent inhibition of CHIKV growth. This molecule effectively inhibited CHIKV replication in the stable embryonal rhabdomyosarcoma cell line capable of producing CHIKV. Our findings demonstrate that the selected compound possesses substantial anti-CHIKV nsP3MD activity both in vitro and in vivo. This work provides a promising molecule for further preclinical studies to develop a potential drug against the CHIKV.

Exploiting the Carboxylate-Binding Pocket of ß-Lactamase Enzymes Using a Focused DNA-Encoded Chemical Library.

ß-Lactamase enzymes hydrolyze and thereby provide bacterial resistance to the important ß-lactam class of antibiotics. The OXA-48 and NDM-1 ß-lactamases cause resistance to the last-resort ß-lactams, carbapenems, leading to a serious public health threat. Here, we utilized DNA-encoded chemical library (DECL) technology to discover novel ß-lactamase inhibitors. We exploited the ß-lactamase enzyme-substrate binding interactions and created a DECL targeting the carboxylate-binding pocket present in all ß-lactamases. A library of 106 compounds, each containing a carboxylic acid or a tetrazole as an enzyme recognition element, was designed, constructed, and used to identify OXA-48 and NDM-1 inhibitors with micromolar to nanomolar potency. Further optimization led to NDM-1 inhibitors with increased potencies and biological activities. This work demonstrates that the carboxylate-binding pocket-targeting DECL, designed based on substrate binding information, aids in inhibitor identification and led to the discovery of novel non-ß-lactam pharmacophores for the development of ß-lactamase inhibitors for enzymes of different structural and mechanistic classes.

Japanese Encephalitis Virus-Infected Cells.

RNA virus infections have been a leading cause of pandemics. Aided by global warming and increased connectivity, their threat is likely to increase over time. The flaviviruses are one such RNA virus family, and its prototypes such as the Japanese encephalitis virus (JEV), Dengue virus, Zika virus, West Nile virus, etc., pose a significant health burden on several endemic countries. All viruses start off their life cycle with an infected cell, wherein a series of events are set in motion as the virus and host battle for autonomy. With their remarkable capacity to hijack cellular systems and, subvert/escape defence pathways, viruses are able to establish infection and disseminate in the body, causing disease. Using this strategy, JEV replicates and spreads through several cell types such as epithelial cells, fibroblasts, monocytes and macrophages, and ultimately breaches the blood-brain barrier to infect neurons and microglia. The neurotropic nature of JEV, its high burden on the paediatric population, and its lack of any specific antivirals/treatment strategies emphasise the need for biomedical research-driven solutions. Here, we highlight the latest research developments on Japanese encephalitis virus-infected cells and discuss how these can aid in the development of future therapies.

Impact of COVID infection on lung function test and quality of life.

Post-COVID-19 pulmonary sequalae are well-recognized early in the pandemic. Survivorship clinics are crucial for managing at-risk patients. However, it is unclear who requires pulmonary function test (PFT) and when PFTs should be performed. We aim to investigate for whom and how these interval PFTs should be performed. We performed a single-centre, prospective cohort study on COVID-19 survivors between 1st May 2020 and 31st April 2022. These patients were followed up at 6, 9 and 12 months with interval PFT and Short Form-36 (SF-36) Health Survey. Those with PFT defects were offered a computed tomography scan of the thorax. Of the 46 patients recruited, 17 (37%) had severe/critical illness. Compared to those with mild/moderate disease, these patients were more likely to experience DLCO defects (59% versus 17%, p = 0.005) and had lower SF-36 scores (mean physical component summary score of 45 ± 12 versus 52 ± 8, p = 0.046). These differences were most notable at 6 months, compared to the 9- and 12-months intervals. DLCO defects were also associated with older age, raised inflammatory markers and extensive CXR infiltrates. Besides interstitial-like abnormalities, obesity and undiagnosed lung conditions accounted for 39% of the PFT abnormalities. Interval PFTs can be performed earliest 6 months post-COVID-19. Patients with normal tests were unlikely to develop new abnormalities and would not require repeat PFTs. Abnormal PFTs can be followed-up with repeat PFTs 6 monthly until resolution. Non-COVID-19 differentials should be considered for persistent PFT abnormalities.

The Use of Platelet-Rich Plasma in the Treatment of Diabetic Foot Ulcers: A Scoping Review.

Platelet-rich plasma (PRP) has been recognized as a method of treatment in medicine since the 1980s. It primarily functions by releasing cytokines and growth factors that promote wound healing; these growth-promoting factors released by PRP enact new processes such as angiogenesis, collagen deposition, and tissue formation that can change wound-healing outcomes. Many studies recognize that PRP aids in chronic wound healing, which is advantageous for patients who suffer from chronic diabetic foot ulcers (DFUs). This scoping review aims to examine the literature to identify the efficacy of PRP use in the healing of DFUs. The objective of this study is to explore whether PRP has a beneficial effect on healing completeness and the rate of healing on DFUs. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched randomized-controlled trials involving PRP use in diabetic patients with foot ulcers using PubMed, Medline, CINAHL Complete, and Cochrane Database of Systematic Reviews. We restricted the search to articles published during 2005-2022, full texts in the English language, articles involving patients aged 19 years or older, articles that used PRP specifically on DFUs, articles that included a control group, and articles with human subjects. The initial search yielded 119 articles after removing duplicates. The final analysis for relevance yielded eight articles. In seven of the eight studies, the PRP group showed significant results, with either faster healing, more complete healing, or a larger percentage of healed participants. In the one study that did not give conclusive evidence of accelerated healing with PRP, PRP was used as an adjunct to fat grafting and only used once. Application styles of PRP for treatment were shown to influence the level of healing in patients, with injected PRP appearing to achieve the best results compared to topical PRP application. However, this was not conclusive due to the involvement of several other variables. Two studies additionally found PRP to be useful in healing refractory DFUs, and one study found that PRP use in patients with additional comorbidities was still more effective in healing DFUs than standard wound control. This study used scoping review methodology with randomized-controlled trials to examine the literature regarding PRP use in the healing of DFUs. The evidence suggests that PRP is a useful tool in reducing healing times and improving rates of complete wound healing in DFUs. There is room for further research in the application styles of PRP before conclusive statements can be made on the efficacy of injected versus topical PRP healing, based on the findings in this study. The results of this review provide a baseline for further research on PRP use in patients with diabetes and can be used by physicians and public health experts to guide future treatment options for DFUs.

Current strategies for the management of psoriasis with potential pharmacological pathways using herbals and immuno-biologicals.

BACKGROUND: Psoriasis is an acute to chronic multifunctional inflammatory skin disorder mediated through T-cell activation, dendritic cell intervention, local vascular variations, atypical keratinocyte proliferation, and neutrophil activation, leading to a skin disorder with no permanent cure. OBJECTIVE: This review aims to find a potent, secure, and dependable medication, with a more scientific examination of herbal resources and recent targeted immunobiological therapies. METHOD: Reports evaluating the effectiveness of biologics & herbal remedies for the topical therapy of psoriasis against control therapies were taken into consideration (placebo or active therapy). The work examined cellular circuits involved in inflammation with its immunogenetic mechanism behind various options available for treating psoriasis in addition to the role of agents inducing psoriasis. RESULTS: The extent of psoriasis can range from small, localized spots to total body coverage, and it can happen at any stage of life. Several theories exist for clarification however, the exact cause of psoriasis is not entirely understood. Researchers have discovered genetic loci linkages, environmental changes, drug induction, lifestyle conditions, some infections, etc. resulting in this disorder. There are numerous known conventional medical treatments for psoriasis, ranging from topical and systemic medicines to phototherapy or combinations of both with recent immunobiological treatment. However, the majority of these treatments are ineffective and have a variety of side effects that limit their long-term usage, such as cutaneous atrophy, tissue toxicity, mutagenicity, and immunosuppression. CONCLUSION: Herbal extracts or isolated compounds can be considered as a substitute for conventional psoriasis treatment. Unfortunately, many investigations often provide a small amount of facts about the safety and effectiveness of topically applied herbal remedies for the treatment of psoriasis. Thus, further factual evidences and validations are needed to promote herbal options, which must be supported by rigorous animal studies or clinical trials using standardised materials and compositions.

DNA-encoded chemical libraries yield non-covalent and non-peptidic SARS-CoV-2 main protease inhibitors.

The development of SARS-CoV-2 main protease (Mpro) inhibitors for the treatment of COVID-19 has mostly benefitted from X-ray structures and preexisting knowledge of inhibitors; however, an efficient method to generate Mpro inhibitors, which circumvents such information would be advantageous. As an alternative approach, we show here that DNA-encoded chemistry technology (DEC-Tec) can be used to discover inhibitors of Mpro. An affinity selection of a 4-billion-membered DNA-encoded chemical library (DECL) using Mpro as bait produces novel non-covalent and non-peptide-based small molecule inhibitors of Mpro with low nanomolar Ki values. Furthermore, these compounds demonstrate efficacy against mutant forms of Mpro that have shown resistance to the standard-of-care drug nirmatrelvir. Overall, this work demonstrates that DEC-Tec can efficiently generate novel and potent inhibitors without preliminary chemical or structural information.

Designing a TiO2-MoO3-BMIMBr nanocomposite by a solvohydrothermal method using an ionic liquid aqueous mixture: an ultra high sensitive acetaminophen sensor.

This study shows a simplistic, efficient procedure to synthesize TiO2-MoO3-BMIMBr nanocomposites. Powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy have all been used to completely analyse the materials. The detection of acetaminophen (AC) has been examined at a modified glassy carbon electrode with TiO2-MoO3-BMIMBr nanocomposites. Moreover, the electrochemical behavior of the nanocomposite modified electrode has been studied by cyclic voltammetry (CV), differential pulse voltammetry (DPV), chronoamperometry and electrochemical impedance spectroscopy (EIS). The linear response of AC was observed in the range 8.26-124.03 nM. The sensitivity and detection limits (S/N = 3) were found to be 1.16 µA L mol-1 cm-2 and 11.54 nM by CV and 24 µA L mol-1 cm-2 and 8.16 nM by DPV respectively.

Barriers of Care to Ovarian Cancer: A Scoping Review.

Ovarian cancer is a leading cause of female cancer-related deaths, but patients continue to be diagnosed late. This subjects them to disease progression and possible death due to lack of early detection, despite earlier stage detection improving survival rates by significant percentages. Early detection and access to care are closely related. However, many barriers to high-quality care exist for patients and the majority of patients do not receive recommended care according to ovarian cancer treatment guidelines. In order to improve care for ovarian cancer patients and decrease healthcare disparities in accessing equitable care, it is important to acknowledge the current gaps in patient knowledge, healthcare availability, and physician practice. This scoping review explores the available evidence on ovarian cancer to identify these barriers to care in the effective treatment of ovarian cancer. Using both inclusion and exclusion criteria, results from the initial literature search were screened by the authors. After quality assessment and screening for relevance, 10 articles were included in the final review. The following themes emerged as barriers to care: hospital and physician-patient volumes, geographic distance from care facilities, patient and physician education, and demographic factors. Many patients were found to not receive guideline adherent care due to various barriers to care, whereas guideline adherent care was independently associated with factors such as patient proximity to a high-volume hospital, White race, and higher socioeconomic status. Several areas were identified as potential for increased patient and physician education, including treatment complications and patient resources. The evidence found that certain socioeconomic groups and racial minorities are often at higher risk for guideline non-adherent care. Additionally, the evidence showed a further need for physicians and healthcare providers to be provided with resources for post-cancer treatment, follow-up, and patient education. The findings of this review will provide health experts and patients with better insight into what barriers may exist so that guideline-adherent care can be better advocated for and met.

Multiplexed Host-Induced Gene Silencing of Aspergillus flavus Genes Confers Aflatoxin Resistance in Groundnut.

Aflatoxins are immunosuppressive and carcinogenic secondary metabolites, produced by the filamentous ascomycete Aspergillus flavus, that are hazardous to animal and human health. In this study, we show that multiplexed host-induced gene silencing (HIGS) of Aspergillus flavus genes essential for fungal sporulation and aflatoxin production (nsdC, veA, aflR, and aflM) confers enhanced resistance to Aspergillus infection and aflatoxin contamination in groundnut (<20 ppb). Comparative proteomic analysis of contrasting groundnut genotypes (WT and near-isogenic HIGS lines) supported a better understanding of the molecular processes underlying the induced resistance and identified several groundnut metabolites that might play a significant role in resistance to Aspergillus infection and aflatoxin contamination. Fungal differentiation and pathogenicity proteins, including calmodulin, transcriptional activator-HacA, kynurenine 3-monooxygenase 2, VeA, VelC, and several aflatoxin pathway biosynthetic enzymes, were downregulated in Aspergillus infecting the HIGS lines. Additionally, in the resistant HIGS lines, a number of host resistance proteins associated with fatty acid metabolism were strongly induced, including phosphatidylinositol phosphate kinase, lysophosphatidic acyltransferase-5, palmitoyl-monogalactosyldiacylglycerol Δ-7 desaturase, ceramide kinase-related protein, sphingolipid Δ-8 desaturase, and phospholipase-D. Combined, this knowledge can be used for groundnut pre-breeding and breeding programs to provide a safe and secure food supply.

Thermodynamics of Azo Dye Adsorption on a Newly Synthesized Titania-Doped Silica Aerogel by Cogelation: A Comparative Investigation with Silica Aerogels and Activated Charcoal.

The adsorption isotherms of azo dyes on a newly synthesized titania-doped silica (TdS) aerogel compared to silica aerogels and activated charcoal (AC) are systematically investigated. Monolithic TdS aerogels were synthesized by the cogelation process followed by supercritical drying of tetraethyl orthosilicate (TEOS) as a gel precursor and titanium(IV) isopropoxide (TTIP) as a metal complex precursor for co-polymerization in ethanol solvent. An acid-base catalyst was used for the hydrolysis and condensation of TEOS and TTIP. The effect of Ti4+ doping in a silica aerogel on the mesoporous structure and the adsorption capacity of methylene blue (MB) and crystal violet (CV) dyes were evaluated from the UV-vis absorption spectra. In order to compare the adsorption isotherms, the surface areas of silica and TdS aerogels were first normalized with respect to AC, as adsorption is a surface phenomenon. The azo dye equilibrium adsorption data were analyzed using different isotherm equations and found to follow the Langmuir adsorption isotherm. The maximum monolayer adsorption capacities for the adsorbent TdS aerogel normalized with the AC of the Langmuir isotherm are 131.58 and 159.89 mg/g for MB and CV dyes, respectively. From the Langmuir curve fitting, the Q max value of the TdS aerogel was found to increase by 1.22-fold compared to AC, while it increased 1.25-1.53-fold compared to the silica aerogel. After four cycles, regeneration efficiency values for MB and CV dyes are about 84 and 80%, respectively. The study demonstrates the excellent potential and recovery rate of silica and TdS aerogel adsorbents in removing dyes from wastewater. The pore volume and average pore size of the new aerogel, TdS, were found to be lower than those of the silica aerogel. Thus, a new TdS aerogel with a high capacity of adsorption of azo dyes is successfully achieved.

Improvement in the Phytochemical Content and Biological Properties of Stevia rebaudiana (Bertoni) Bertoni Plant Using Endophytic Fungi Fusarium fujikuroi.

This study aimed to increase the therapeutic potential of medicinal plants through inoculation with endophytic fungi. As endophytes influence medicinal plants' biological properties, twenty fungal strains were isolated from the medicinal plant Ocimum tenuiflorum. Among all fungal isolates, the R2 strain showed the highest antagonistic activity towards plant pathogenic fungi Rosellinia necatrix and Fusarium oxysporum. The partial ITS region of the R2 strain was deposited in the GenBank nucleotide sequence databases under accession number ON652311 as Fusarium fujikuroi isolate R2 OS. To ascertain the impact of an endophytic fungus on the biological functions of medicinal plants, Stevia rebaudiana seeds were inoculated with Fusarium fujikuroi (ON652311). In the DPPH assay, the IC50 value of the inoculated Stevia plant extracts (methanol, chloroform, and positive control) was 72.082 µg/mL, 85.78 µg/mL, and 18.86 µg/mL, respectively. In the FRAP assay, the IC50 value of the inoculated Stevia extracts (methanol, chloroform extract, and positive control) was 97.064 µM Fe2+ equivalents, 117.662 µM Fe2+ equivalents, and 53.384 µM Fe2+ equivalents, respectively. In the extracts of the plant inoculated with endophytic fungus, rutin and syringic acid (polyphenols) concentrations were 20.8793 mg/L and 5.4389 mg/L, respectively, which were higher than in the control plant extracts. This approach can be further utilized for other medicinal plants to increase their phytochemical content and hence medicinal potential in a sustainable way.

Glucocorticoid use in rheumatoid arthritis patients and the onset of pneumonia: a systematic review and meta-analysis.

CONTEXT: Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly affects joints. Although many treatment options exist, the most common, disease-modifying antirheumatic drugs (DMARDs), have been associated with pulmonary infections. These types of infections (specifically pneumonia) can be detrimental to RA patients. This leads providers to utilize other treatment modalities such as glucocorticoids (GCs). GCs are commonly utilized to treat RA; however, the role of GCs in the onset of pneumonia in RA patients is not fully understood. OBJECTIVES: The goal of this study was to systematically review and statistically analyze pooled data documenting pneumonia as an adverse event in RA patients on DMARDs as a monotherapy vs RA patients on DMARDs and GCs as combination therapy utilizing the Population, Intervention, Comparison, and Outcomes (PICO) framework. METHODS: On August 1, 2021, a search was conducted and completed on six databases: Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, International Pharmaceutical Abstracts (IPA), and ClinicalTrials.gov. A total of 12 researchers were involved with the search and screening of articles (K.E., P.R.; V.A., D.P.C.; C.B., D.C.; T.A., E.S.; S.H., L.B.; K.S., C.S.). Search terms were identified utilizing Medical Subject Headings (MeSH) and Emtree and included "glucocorticoids," "rheumatoid arthritis," "pneumonia," and "respiratory tract infections," Inclusion criteria included human subjects over the age of 18 with seropositive RA, on a combination of GC (prednisone, methylprednisolone, or prednisolone) with DMARD (methotrexate [MTX], hydroxychloroquine [HCQ], or sulfasalazine [SSZ]) and developed pneumonia of bacterial, viral, or fungal origin. The control groups were on a DMARD monotherapy regimen. Articles were excluded if they were not in English, had less than 20 participants, were case reports or literature reviews, included animal subjects, and did not adhere to the established PICO framework. Five teams of two researchers individually sorted through abstracts of articles based on the inclusion and exclusion criteria. The same teams individually sorted through full-text articles of selected abstracts based on the same criteria. Conflicts between each team were resolved by a separate researcher. Odds ratios were utilized to quantify the effect sizes of combined studies from a random effects model. Chi-square tests and I2 statistics were utilized to analyze heterogeneity. RESULTS: A total of 3360 articles were identified from all databases, and 416 duplicate articles were removed. Thus, a total of 2944 articles abstracts were screened, of which 2819 articles either did not meet the inclusion criteria or did meet the exclusion criteria. A total of 125 articles were retrieved and assessed for full-text eligibility, of which only three observational articles were included for meta-analysis. Statistical results revealed that patients treated with DMARDs monotherapy are 95% (95% CI: 0.65-0.99) less likely to develop pneumonia compared to patients treated with a DMARD and GCs (p=0.002). CONCLUSIONS: Our data suggest that RA patients have a higher probability of developing pneumonia on combination therapy with GCs, compared to monotherapy with DMARDs. To our knowledge, our findings are the first to systematically review and statistically evaluate the relationship between the use of GCs and show an increased chance of developing pneumonia.

Artificial Intelligence Assisted Fabrication of 3D, 4D and 5D Printed Formulations or Devices for Drug Delivery.

5D & 4D printings are an advanced version of 3D printing class and are one of the most revolutionary and powerful fabrication methods used for preparing innovative structures and solid substances using precise additive manufacturing technology. It captures the imagination of one with its potential to produce flexible designing and fabrication of innovative products with high complexity and speed. This technology with the assistance of AI (Artificial Intelligence) facilitates real-time sensing, adapting to change, and predicting the state of printing. 3D printing works by employing advanced materials utilizing a computer aided design with tomography scan under AI control which deposits printing material in accordance with the nature of a file usually in STL format, but it requires time for printing. This shortcoming can be overcome by 4D printing where smart materials are incorporated with time as 4th dimension. This technique has self-repair and self-assembly properties that will save around 80% of time. Some printed materials are made sensitive to temperature, humidity, light, and other parameters so that they can respond to stimulus, but it's one limitation of not being able to print complex shapes having curved surfaces can be overcome by utilising 5D printing where additive manufacturing is done by rotation of extruder head and rotation of print bed to print in 5 different axes. This review evaluates the prospective of these techniques with AI interference in medicine and pharmacy, with its effective and efficient production for the required design precision.

Effect of moderate intensity resistance training with blood flow restriction on muscle strength and girth in young adults - a randomized control trial.

OBJECTIVES: To examine the effects of moderate intensity resistance training with blood flow restriction on muscle strength and forearm girth. METHODS: Total of 39 students enrolled in this study were divided into three groups that is group A (control group), group B and group C. Group A performed exercise training without restrictive pressure, group B and C performed exercise training with 50 and 75 mmHg respectively. Both the outcome measures were evaluated on day 1 and day 12th with the help of digital dynamometer and measuring tape. RESULTS: Repeated measure ANOVA with Post hoc analysis was done using SPSS software version 20. The result of the study showed significant (p≤0.05) within subject improvement in muscle strength and muscle girth in all the three groups. However, significant improvement in muscle strength was found in between group analysis (p≤0.05). CONCLUSIONS: The results of the study can be concluded as the partial blood flow restriction (50 mmHg) with moderate intensity resistance training resulted in greater handgrip strength than the other two groups. No difference was found in forearm girth among the three groups, however within the group difference was found.

Comparing the Efficacy of Dynamic Neuromuscular Stabilization Exercises and Kegel Exercises on Stress Urinary Incontinence in Women: A Pilot Study.

Background and objective Stress urinary incontinence (SUI) is a prevalent condition affecting women of various age groups, significantly impacting their quality of life. To address this multifaceted issue, a comprehensive approach that goes beyond traditional pelvic floor exercises is needed. Dynamic neuromuscular stabilization (DNS) exercises, targeting the integrated spinal stabilization system, offer a promising alternative. Thus, this study aimed to compare the effectiveness of DNS exercises and Kegel exercises in managing SUI among women. Methods This single-blinded, pilot study involved 24 women aged 18-40 years with mild to moderate SUI. Participants were divided into DNS and Kegel exercise groups. Outcome measures included perineometer readings, electromyography (EMG) data, and the Urogenital Distress Inventory-6 (UDI-6). Statistical analysis compared baseline and 12-week data within and between groups, and rank-biserial correlation coefficient (r) as a measure of effect size in our study was calculated. Results At 12 weeks, the DNS group showed significant improvement in pelvic floor muscle strength compared to Kegel exercises (p = 0.005). Both groups had significantly enhanced pelvic floor muscle strength (p < 0.05). A significant change occurred for EMG average, EMG peak, and EMG maximum voluntary contraction (MVC) at 12 weeks (average p = 0.005; peak p = 0.001; MVC p = 0.009), with significant improvements in both groups (p < 0.05). For UDI-6, a significant difference emerged between the two groups at 12 weeks (p < 0.05), with significant improvements in both groups individually from baseline to 12 weeks (p < 0.05). The effect size "r" for all variables indicated a medium to large effect size, underscoring the substantial and significant impact of DNS exercises in managing SUI among women compared to Kegel exercises. Conclusion This study suggests that DNS exercises, emphasizing the coordinated activation of the diaphragm, abdominals, multifidus, and pelvic floor, may provide a more effective approach for managing SUI in women compared to traditional Kegel exercises.

Dosimetric Comparison of Unmatched Flattening Filter-free and Flattened Beams in Volumetric Arc Therapy Plans for Head-and-neck Cancer.

Introduction: Conventionally, the fattened beam is being used in radiotherapy for routine clinical cases even after introduction of intensity-modulated radiotherapy with incorporation of multi-leaf collimator system. With the removal of the flattening filter (FF) from the beam's path average energy of the photon gets reduced resulting in reduced scatter, reduction in treatment time, and reduced neutron contamination for high-energy beam and ultimately resulting in treatment plan quality deviations. This study aims to investigate the usefulness of the FF-free (FFF) beam for routine head-and-neck cancer (HNC) cases treated with volumetric arc therapy (VMAT) and dosimetrically compares the result with the FF beam. Materials and Methods: In this study, 20 patients treated on HalcyonTM (unmatched 6 megavoltage [6MV] FFF beam) medical linear accelerator with VMAT of different HNC selected and for comparison with 6MV FF beam, 20 equivalent treatment plans are created for TruebeamTM configuration and the plans have been evaluated for target coverage, doses to the organ at risk (OAR), and other dose quality indices. Results: Comparable target coverage, doses to OARs except for rest right parotid (P = 0.02) between 6MV FFF beam and 6MV FF beam is observed. Insignificant differences in conformity index, homogeneity index, and gradient index have been observed. Higher monitor unit (MU) (P ≤ 0.001) and lesser beam on time (BOT) (P = 0.003) have been observed in 6MV FFF. Conclusion: 6MV FFF beam provides comparable target coverage and improved dose-sparing effect to most of the OARs. 6MV FFF beam has lesser BOT, but on the other hand number of MUs is higher as compared to 6MV-FF plans.