Smart laser Sintering: Deep Learning-Powered powder bed fusion 3D printing in precision medicine.

Medicines remain ineffective for over 50% of patients due to conventional mass production methods with fixed drug dosages. Three-dimensional (3D) printing, specifically selective laser sintering (SLS), offers a potential solution to this challenge, allowing the manufacturing of small, personalized batches of medication. Despite its simplicity and suitability for upscaling to large-scale production, SLS was not designed for pharmaceutical manufacturing and necessitates a time-consuming, trial-and-error adaptation process. In response, this study introduces a deep learning model trained on a variety of features to identify the best feature set to represent drugs and polymeric materials for the prediction of the printability of drug-loaded formulations using SLS. The proposed model demonstrates success by achieving 90% accuracy in predicting printability. Furthermore, explainability analysis unveils materials that facilitate SLS printability, offering invaluable insights for scientists to optimize SLS formulations, which can be expanded to other disciplines. This represents the first study in the field to develop an interpretable, uncertainty-optimized deep learning model for predicting the printability of drug-loaded formulations. This paves the way for accelerating formulation development, propelling us into a future of personalized medicine with unprecedented manufacturing precision.

Age-Dependent Abundance of CYP450 Enzymes Involved in Metronidazole Metabolism: Application to Pediatric PBPK Modeling.

The expression of cytochrome P450 (CYP) enzymes is highly variable and associated with factors, such as age, genotype, sex, and disease states. In this study, quantification of metronidazole metabolizing CYP isoforms (CYP2A6, CYP2E1, CYP3A4, CYP3A5, and CYP3A7) in human liver microsomes from 115 children and 35 adults was performed using a quantitative proteomics method. The data confirmed age-dependent increase in CYP2A6, CYP2E1, and CYP3A4 abundance, whereas, as expected, CYP3A7 abundance showed postnatal decrease with age. In particular, the fold difference (neonatal to adulthood levels) in the protein abundance of CYP2A6, CYP2E1, and CYP3A4 was 14, 11, and 20, respectively. In contrast, protein abundance of CYP3A7 was > 125-fold higher in the liver microsomes of neonates than of adults. The abundance of CYP2A6 and CYP3A5 was associated with genotypes, rs4803381 and rs776746, respectively. A proteomics-informed physiologically based pharmacokinetic (PBPK) model was developed to describe the pharmacokinetics of metronidazole and its primary metabolite, 2-hydroxymethylmetronidazole. The model revealed an increase in the metabolite-to-parent ratio with age and showed a strong correlation between CYP2A6 abundance and metabolite formation (r2 = 0.75). Notably, the estimated contribution of CYP3A7 was ~ 75% in metronidazole clearance in neonates. These data suggest that variability in CYP2A6 and CYP3A7 in younger children poses the risk of variable pharmacokinetics of metronidazole and its active metabolite with a potential impact on drug efficacy and safety. No sex-dependent difference was observed in the protein abundance of the studied CYPs. The successful integration of hepatic CYP ontogeny data derived from a large liver bank into the pediatric PBPK model of metronidazole can be extended to other drugs metabolized by the studied CYPs.

Exploring the interactions of JAK inhibitor and S1P receptor modulator drugs with the human gut microbiome: Implications for colonic drug delivery and inflammatory bowel disease.

The gut microbiota is a complex ecosystem, home to hundreds of bacterial species and a vast repository of enzymes capable of metabolising a wide range of pharmaceuticals. Several drugs have been shown to affect negatively the composition and function of the gut microbial ecosystem. Janus Kinase inhibitors and Sphingosine-1-phosphate receptor modulators are drugs recently approved for inflammatory bowel disease through an immediate release formulation and would potentially benefit from targeted colonic targeted delivery to enhance the local drug concentration at the diseased site. However, their impact on the human gut microbiota and susceptibility to bacterial metabolism remain unexplored. With the use of calorimetric, optical density measurements, and metagenomics next-generation sequencing, we show that JAK inhibitors have a minor impact on the composition of the human gut microbiota, while ozanimod exerts a significant antimicrobial effect, leading to a prevalence of the Enterococcus genus and a markedly different metabolic landscape when compared to the untreated microbiota. Moreover, ozanimod is the only drug subject to enzymatic degradation by the human gut microbiota sourced from six healthy donors.. Overall, given the crucial role of the gut microbiome in health, screening assays to investigate the interaction of drugs with the microbiome should be encouraged for the pharmaceutical industry as a standard in the drug discovery and development process.

USP11 modulates mitotic progression and senescence by regulating the p53-p21 axis through MDM2 deubiquitination.

USP11 is overexpressed in colorectal cancer (CRC) and breast cancer tissues compared to normal tissues, suggesting a role in promoting cell proliferation and inhibiting cell death. In this study, we observed that depleting USP11 inhibits cell proliferation and delays cell cycle progression. This depletion leads to increased p53 protein levels due to an extended half-life, resulting in elevated p21 mRNA levels in a p53-dependent manner. The rise in p53 protein upon USP11 depletion is linked to a reduced half-life of MDM2, a known E3 ligase for p53, via enhanced polyubiquitination of MDM2. These findings indicate that USP11 might act as a deubiquitinase for MDM2, regulating the MDM2-p53-p21 axis. Additionally, USP11 depletion promotes the induction of senescent cells in a manner dependent on its deubiquitinase activity. Our findings provide insights into the physiological significance of high USP11 expression in primary tumors and its reduction in senescent cells, highlighting its potential as a therapeutic target.

Developing an innovative 3D printing platform for production of personalised medicines in a hospital for the OPERA clinical trial.

Breast cancer is the most frequently diagnosed cancer in women worldwide, and non-adherence to adjuvant hormonotherapy can negatively impact cancer recurrence and relapse. Non-adherence is associated with side effects of hormonotherapy. Pharmacological strategies to mitigate the side effects include coadministration of antidepressants, however patients remain non-adherent. The aim of this work was to develop medicines containing both hormonotherapy, tamoxifen (20 mg), along with anti-depressants, either venlafaxine (37.5 or 75 mg) or duloxetine (30 or 60 mg), to assess the acceptability and efficacy of this personalised approach for mitigating tamoxifen side effects in a clinical trial. A major criterion for the developed medicines was the production rate, specified at minimum 200 dosage units per hour to produce more than 40,000 units required for the clinical trial. A novel capsule filling approach enabled by the pharmaceutical 3D printer M3DIMAKER 2 was developed for this purpose. Firstly, semi-solid extrusion 3D printing enabled the filling of tamoxifen pharma-ink prepared according to French compounding regulation, followed by filling of commercial venlafaxine or duloxetine pellets enabled by the development of an innovative pellet dispensing printhead. The medicines were successfully developed and produced in the clinical pharmacy department of the cancer hospital Gustave Roussy, located in Paris, France. The developed medicines satisfied quality and production rate requirements and were stable for storage up to one year to cover the duration of the trial. This work demonstrates the feasibility of developing and producing combined tamoxifen medicines in a hospital setting through a pharmaceutical 3D printer to enable a clinical trial with a high medicines production rate requirement.

Gestational diabetes mellitus as a risk factor for future Type-2 diabetes mellitus: An experience from a tertiary care diabetes hospital, Karachi - Pakistan.

Objective: To evaluate the history of gestational diabetes mellitus and other risk factors in women presenting with Type-2 diabetes mellitus at a tertiary care hospital. Methods: This cross-sectional study was carried out at Baqai Institute of Diabetology & Endocrinology (BIDE), Baqai Medical University (BMU), Karachi-Pakistan from July 2019 to May 2022. Women with Type-2 diabetes mellitus (T2DM) visiting outpatient department of BIDE with a previous history of GDM were recruited. Details were obtained on pre-designed questionnaire after taking informed written consent. Results: A total of 378 women who had a prior history of GDM were included. Mean age (years) was 43.53±10.17. Mostly women were obese (BMI = 30.53±6.08) and have sedentary lifestyle. Mean HbA1c (%) was 9.08±2.24. This study found family history of T2DM and hypertension were common risk factors in women with GDM history. Mostly, women were diagnosed as GDM during 2nd trimester 153(42%) and was mainly seen in multiparous women (occur in 4th and above pregnancy). We found hypertension as common complication during pregnancy. Around 46% women developed T2DM within one year of GDM diagnosis, and 29.6% between one to five years. Conclusion: Majority of women with GDM developed T2DM within five years of diagnosis. The potential associated risk factors were age, family history of diabetes, insulin use during pregnancy, trimester of GDM diagnosis, and hypertension during pregnancy. Awareness and life style modifications along with regular post-partum follow up with screening for T2DM should be part of GDM management to prevent or delay the occurrence of this serious complication.

Rotavirus genotype dynamics in Pakistan: G9 and G12 emerging as dominant strains in vaccinated children (2019).

Rotavirus A (RVA) is a leading cause of severe gastroenteritis in children worldwide, and vaccination has become a pivotal strategy to reduce the associated morbidity and mortality. This study presents a molecular characterization of RVA genotypes circulating among vaccinated children in Pakistan during the year 2019. A total of 510 stool samples were collected from children of up to five years of age presenting with acute gastroenteritis symptoms in Rawalpindi, Islamabad regions of Pakistan. The RVA antigen was detected using ELISA on these samples. RVA G/P genotyping was performed on ELISA positive samples using Multiplex semi-nested reverse transcriptase PCR. RVA was found in 130 fecal samples, with an overall prevalence of 25.4 %. G9P[8] (20 %) is the most prevalent genotype, followed by G12P[6] (17 %), G3P[8] (14 %), G1P[8] (12 %), G2P[4] (10 %), G12P[8] (7 %), G9P[6] (7 %), G3P[6] (6 %), G3P[4] (4 %) and G1P[6] (3 %) respectively. There is a statistically significant difference (p < 0.05) found in the group age (in months) of RVA gastroenteritis cases as detected by RT-PCR. The highest number of positive cases was found in the age range from 0 to 6 months, followed by 7-12 months, 13-24 months, and 25-60 months, respectively. Dehydration is statistically significantly associated (p˂ 0.05) in RVA gastroenteritis cases compared to those who tested negative. This study emphasizes the significance of maintaining a continuous surveillance system and conducting genomic analysis of RVA genotypes in children upto the age of 5 years. This is essential for tracking the circulation of RVA genotypes. The results from this research enhance our comprehension of how RVA genotypes are changing over time in Pakistan, underscoring the ongoing necessity for improving vaccine coverage and effectiveness. This, in turn, can help reduce the impact of RVA-related illnesses in children.

Thermoelectric Transport Performance in p-Type AgSbTe2-Based Materials through Entropy Engineering.

Being a major obstacle, Ag2Te has always been restricted in p-type AgSbTe2-based materials to improve their thermoelectric performance. This work reveals a stabilized AgSbTe2 through Sn/Ge alloying as synthesized by melting, annealing, and hot press. Interestingly, addition of Sn/Ge in AgSbTe2 extended the solubility limit up to ∼30% and hence suppressed Ag2Te in Ag(1-x)SnxSb(1-y)GeyTe2 compounds and led to enhanced electrical transport. Moreover, electrical and thermal transport properties of AgSbTe2 have been greatly affected by the phase transition of Ag2Te near 425 K. However, high-entropy Ag0.85Sn0.15Sb0.85Ge0.15Te2 compound results in a stabilized rock-salt structure and presents a high power factor of ∼10.8 µW cm-1 K-2 at 757 K. Besides, density functional theory reveals that available multivalence bands in Sn/Ge-doped AgSbTe2 lead to reduction in energy offsets. Meanwhile, a variety of defects appear in the Ag0.85Sn0.15Sb0.85Ge0.15Te2 sample due to entropy change, and thus lattice thermal conductivity decreases. Ultimately, a high figure of merit of ∼1.5 is attained at 757 K. This work demonstrates a roadmap for other group IV-VI materials so that the high-entropy approach may inhibit the impurity phases with extended solubility limit and result in high thermoelectric performance.

3D printed dispersible efavirenz tablets: A strategy for nasogastric administration in children.

Enteral feeding tubes (EFTs) can be placed in children diagnosed with HIV which need nutritional support due to malnutrition. EFTs are the main route for medication administration in these patients, bringing up concerns about off label use of medicines, dose inaccuracy and tube clogging. Here we report for the first time the use of selective laser sintering (SLS) 3D printing to develop efavirenz (EFZ) dispersible printlets for patients with HIV that require EFT administration. Water soluble polymers Parteck® MXP and Kollidon® VA64 were used to obtain both 500 mg (P500 and K500) and 1000 mg printlets (P1000 and K1000) containing 200 mg of EFZ each. The use of SLS 3D printing obtained porous dosage forms with high drug content (20 % and 40 % w/w) and drug amorphization using both polymers. P500, K500 and K1000 printlets reached disintegration in under 230 s in 20 mL of water (25 ± 1 °C), whilst P1000 only partially disintegrated, possibly due to saturation of the polymer in the medium. As a result, the development of dispersible EFZ printlets using hydrophilic polymers can be explored as a potential strategy for drug delivery through EFTs in paediatrics with HIV, paving the way towards the exploration of more rapidly disintegrating polymers and excipients for SLS 3D printing.

Untargeted metabolomics, optimization of microwave-assisted extraction using Box-Behnken design and evaluation of antioxidant, and antidiabetic activities of sugarcane bagasse.

INTRODUCTION: The fruit wastes, in particular agricultural wastes, are considered potential and inexpensive sources of bioactive compounds. OBJECTIVE: The current study was aimed at the preparation of an optimized extract of sugarcane bagasse using microwave-assisted extraction (MAE) technology and comparative evaluation of chemical composition, antioxidant, and antidiabetic activities with extract prepared through maceration technique. METHODOLOGY: Box-Behnken Design (BDD) with response surface methodology was applied to observe interactions of three independent variables (ethanol concentrations [%], microwave power [W], and extraction time [min]) on the dependent variables (total phenolic content [TPC] and antioxidant status via 2,2-diphenyl-1-picrylhydrazyl [DPPH] to establish optimal extraction conditions. The ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) analysis was applied for untargeted metabolite profiling, and in vitro assays were used for evaluation of the antidiabetic and antioxidant potential of the extract. Moreover, an in silico study was used to predict the interaction of five dominant compounds from the UHPLC-Q-TOF-MS profile against the dipeptidyl peptidase-IV (DPP-IV) enzyme. RESULTS: The optimal conditions for the extraction were established at 60% (v/v) ethanol, 500 W microwave power, and 5 min time with TPC 12.83 ± 0.66 mg GAE/g d.w. and DPPH 45.09 ± 0.07%. The UHPLC-Q-TOF-MS analysis revealed the presence of a total of 106 compounds in the extract. Moreover, the extract prepared through MAE technology presented higher TPC and DPPH findings than the extract prepared through maceration. Similarly, the extract was also found with good antidiabetic activity by inhibiting the DPP-IV enzyme which was also rectified theoretically by a molecular docking study. CONCLUSION: The current study presents a sustainable and an optimized approach for the preparation of sugarcane bagasse extract with functional phytoconstituents and higher antidiabetic and antioxidant activities.

Can in vitro/in silico tools improve colonic concentration estimations for oral extended-release formulations? A case study with upadacitinib.

Upadacitinib, classified as a highly soluble drug, is commercially marketed as RINVOQ®, a modified-release formulation incorporating hydroxypropyl methylcellulose as a matrix system to target extended release throughout the gastrointestinal (GI) tract. Our study aimed to explore how drug release will occur throughout the GI tract using a plethora of in vitro and in silico tools. We built a Physiologically-Based Pharmacokinetic (PBPK) model in GastroPlus™ to predict the systemic concentrations of the drug when administered using in vitro dissolution profiles as input to drive luminal dissolution. A series of in vitro dissolution experiments were gathered using the USP Apparatus I, III and IV in presence of biorelevant media, simulating both fasted and fed state conditions. A key outcome from the current study was to establish an in vitro-in vivo correlation (IVIVC) between (i) the dissolution profiles obtained from the USP I, III and IV methods and (ii) the fraction absorbed of drug as deconvoluted from the plasma concentration-time profile of the drug. When linking the fraction dissolved as measured in the USP IV model, a Level A IVIVC was established. Moreover, when using the different dissolution profiles as input for PBPK modeling, it was also observed that predictions for plasma Cmax and AUC were most accurate for USP IV compared to the other models (based on predicted versus observed ratios). Furthermore, the PBPK model has the utility to extract the predicted concentrations at the level of the colon which can be of utmost interest when working with specific in vitro assays.

Load frequency stabilization of distinct hybrid conventional and renewable power systems incorporated with electrical vehicles and capacitive energy storage.

Maintaining a power balance between generation and demand is generally acknowledged as being essential to maintaining a system frequency within reasonable bounds. This is especially important for linked renewable-based hybrid power systems (HPS), where disruptions are more likely to occur. This paper suggests a prominent modified "Fractional order-proportional-integral with double derivative (FOPIDD2) controller" as an innovative HPS controller in order to navigate these obstacles. The recommended control approach has been validated in power systems including wind, reheat thermal, solar, and hydro generating, as well as capacitive energy storage and electric vehicle. The improved controller's performance is evaluated by comparing it to regular FOPID, PID, and PIDD2 controllers. Furthermore, the gains of the newly structured FOPIDD2 controller are optimized using a newly intended algorithm terms as squid game optimizer (SGO). The controller's performance is compared to benchmarks such as the grey wolf optimizer (GWO) and jellyfish search optimization. By comparing performance characteristics such as maximum frequency undershoot/overshoot, and steadying time, the SGO-FOPIDD2 controller outperforms the other techniques. The suggested SGO optimized FOPIDD2 controller was analyzed and validated for its ability to withstand the influence of power system parameter uncertainties under various loading scenarios and situations. Without any complicated design, the results show that the new controller can work steadily and regulate frequency with an appropriate controller coefficient.

Study loss of vegetative cover and increased land surface temperature through remote sensing strategies under the inter-annual climate variability in Jinhua-Quzhou basin, China.

The Jinhua-Quzhou basin in China is one of the most susceptible areas to drought. Due to the loss of vegetation and great fluctuations in rainfall and surface temperature, global warming occurs. Timely, accurate, and effective drought monitoring is crucial for protecting local vegetation and determining which vegetation is most vulnerable to increased LST during the period 1982-2019. It assumes a strong correlation between loss of vegetation cover, changes in monsoon climate, drought, and increases in land surface temperature (LST). Due to significantly increased in LST, low precipitation and vegetation cover, NDVI, TVDI, VCI, and NAP are useful in characterizing drought mitigation strategies. The temperature vegetation drought index (TVDI), normalized difference vegetation index (NDVI), vegetation condition index (VCI), and monthly precipitation anomaly percentage (NAP) can be helped to characterize drought reduction strategies. Monthly NDVI, NAP, VCI, TVDI, normalized vegetation supply water index (NVSWI), temperature condition index (TCI), vegetation health index (VHI), and heat map analysis indicate that the Jinhua-Quzhou basin experienced drought during 1984, 1993, 2000, and 2011. Seasonal SR, WVP, WS, NDVI, VCI, and NAP charts confirm that the Jinhua-Quzhou basin was affected by severe drought in 1984, which continued and led to severe droughts in 1993, 2000, and 2011. Regression analysis showed a significant positive correlation between NDVI, TVDI, VCI, and NAP values, while NVSWI, TVDI, and VHI showed positive signs of good drought monitoring strategies. The research results confirm the correlation between loss of vegetation cover and LST, which is one of the causes of global warming. The distribution of drought changed a trend indicating that compared with the Jinhua region; the Quzhou region has more droughts. The changing trend of drought has characteristics from 1982 to 2019, and there are significant differences in drought changing trends between different Jinhua-Quzhou basin areas. Overall, from 1982 to 2019, the frequency of drought showed a downward trend. We believe that these results will provide useful tools for drought management plans and play a relevant role in mitigating the effects of drought and protecting humanity from climate hazards.

Paediatric clinical study of 3D printed personalised medicines for rare metabolic disorders.

Rare diseases are infrequent, but together they affect up to 6-10 % of the world's population, mainly children. Patients require precise doses and strict adherence to avoid metabolic or cardiac failure in some cases, which cannot be addressed in a reliable way using pharmaceutical compounding. 3D printing (3DP) is a disruptive technology that allows the real-time personalization of the dose and the modulation of the dosage form to adapt the medicine to the therapeutic needs of each patient. 3D printed chewable medicines containing amino acids (citrulline, isoleucine, valine, and isoleucine and valine combinations) were prepared in a hospital setting, and the efficacy and acceptability were evaluated in comparison to conventional compounded medicines in six children. The inclusion of new flavours (lemon, vanilla and peach) to obtain more information on patient preferences and the implementation of a mobile app to obtain patient feedback in real-time was also used. The 3D printed medicines controlled amino acid levels within target levels as well as the conventional medicines. The deviation of citrulline levels was narrower and closer within the target concentration with the chewable formulations. According to participants' responses, the chewable formulations were well accepted and can improve adherence and quality of life. For the first time, 3DP enabled two actives to be combined in the same formulation, reducing the number of administrations. This study demonstrated the benefits of preparing 3D printed personalized treatments for children diagnosed with rare metabolic disorders using a novel technology in real clinical practice.

The colon targeting efficacies of mesalazine medications and their impacts on the gut microbiome.

Successful treatment of ulcerative colitis (UC) is highly dependent on several parameters, including dosing regimen and the ability to deliver drugs to the disease site. In this study two strategies for delivering mesalazine (5-aminosalicylic acid, 5-ASA) to the colon were compared in an advanced in vitro model of the human gastrointestinal (GI) tract, the SHIME® system. Herein, a prodrug strategy employing bacteria-mediated drug release (sulfasalazine, Azulfidine®) was evaluated alongside a formulation strategy that utilised pH and bacteria-mediated release (5-ASA, Octasa® 1600 mg). SHIME® experiments were performed simulating both the GI physiology and colonic microbiota under healthy and inflammatory bowel disease (IBD) conditions, to study the impact of the disease state and ileal pH variability on colonic 5-ASA delivery. In addition, the effects of the products on the colonic microbiome were investigated by monitoring bacterial growth and metabolites. Results demonstrated that both the prodrug and formulation approaches resulted in a similar percentage of 5-ASA recovery under healthy conditions. On the contrary, during experiments simulating the GI physiology and microbiome of IBD patients (the target population) the formulation strategy resulted in a higher proportion of 5-ASA delivery to the colonic region as compared to the prodrug approach (P < 0.0001). Interestingly, the two products had distinct effects on the synthesis of key bacterial metabolites, such as lactate and short chain fatty acids, which varied according to disease state and ileal pH variability. Further, both 5-ASA and sulfasalazine significantly reduced the growth of the faecal microbiota sourced from six healthy humans. The findings support that the approach selected for colonic drug delivery could significantly influence the effectiveness of UC treatment, and highlight that drugs licensed for UC may differentially impact the growth and functioning of the colonic microbiota.

A novel output feedback consensus control approach for generic linear multi-agent systems under input saturation over a directed graph topology.

This paper considers an output feedback consensus control approach for the generic linear multi-agent systems (MASs) under input saturation over a directed graph. A region of stability-based approach has been established for dealing with the input saturation. A conventional Luenberger observer for estimating the states of followers by themselves and an advanced cooperative observer for estimating the state of leader by followers have been applied for an estimated state feedback control. The stability conditions have been derived by considering a three-term-based combined Lyapunov function. Moreover, computationally simple controller and estimator design conditions have been obtained by resorting to a decoupling approach A set of initial conditions has been investigated to achieve the leader-following consensus of MASs under the input saturation constraint. To the best of our knowledge, an output feedback consensus approach, providing a consensus region, for generic linear MASs under input saturation over directed graphs without requiring the exact state of the leader has been explored for the first time. In contrast to the existing methods, the proposed approach considers an output feedback approach (rather than the state feedback), accounts for both linear and nonlinear saturation regions, applies an estimate of the state of the leader through cooperative observer, and is based on a generalized sector condition for the saturation nonlinearity. In addition, it offers a computationally simple design solution owing to the proposed decoupling method. Simulation results are provided to validate the efficacy of the designed protocol for F-18 aircraft and unmanned ground vehicles.

Epiglottic capillary hemangioma in an adult female: A rare case report.

INTRODUCTION AND IMPORTANCE: Capillary hemangioma of larynx can occur in both pediatric and adult population. However, epiglottic capillary hemangioma in adults is a very rare presentation. Its pathophysiological basis involves self limiting and self expanding vascularization and it is a characteristically well delineated benign mass. CASE PRESENTATION: Here we present a case of a 40-year-old female who presented with complaint of per oral bleed in spitting which was about a teaspoon in quantity since 1 month. There was no associated hoarseness, dysphagia, respiratory distress, hemoptysis or neck swelling. There were no other systemic manifestations i.e. weight loss, fatigue or anemia. There was no familial history. CLINICAL DISCUSSION: On examination, Indirect Laryngoscopy (IDL) revealed a mass on the posterior surface of epiglottis. 70° view endoscope confirmed the findings of IDL. All other neighboring structures i.e. vocal cords, anterior and posterior commissures and pyriform fossa were normal and no mass or pathology was seen. Imaging studies contrast enhanced CT scan of neck soft tissue window showed isodense opacity in supraglottic region. Surgical excision and hemostasis were carried out using Colorado bipolar cauterization. The histopathological investigation of the mass revealed a benign lesion compatible with capillary hemangioma. CONCLUSION: As until now, no case of capillary hemangioma of epiglottis has been reported, head and neck surgeons are not well aware of this case. This case report will add valuable insight to the relative surgeons/clinicians.

Customizable orodispersible films: Inkjet printing and data matrix encoding for personalized hydrocortisone dosing.

The aim of this study was to exploit the versatility of inkjet printing to develop flexible doses of drug-loaded orodispersible films that encoded information in a data matrix pattern, and to introduce a specialised data matrix-generator software specifically focused on the healthcare sector. Pharma-inks (drug-loaded inks) containing hydrocortisone (HC) were developed and characterised based on their rheological properties and drug content. Different strategies were investigated to improve HC solubility: formation of ß-cyclodextrin complexes, Soluplus® based micelles, and the use of co-solvent systems. The software automatically adapted the data matrix size and identified the number of layers for printing. HC content deposited in each film layer was measured, and it was found that the proportion of co-solvent used directly affected the drug solubility and simultaneously played a role in the modification of the viscosity and surface tension of the inks. The formation of ß-cyclodextrin complexes improved the drug quantity deposited in each layer. On the contrary, micelle-based inks were not suitable for printing. Orodispersible films containing flexible and low doses of personalised HC were successfully prepared, and the development of a code generator software oriented to medical use provided an additional, innovative, and revolutionary advantage to personalised medicine safety and accessibility.

Poly(D,l-lactide-co-glycolide) particles are metabolised by the gut microbiome and elevate short chain fatty acids.

The production of short chain fatty acids (SCFAs) by the colonic microbiome has numerous benefits for human health, including maintenance of epithelial barrier function, suppression of colitis, and protection against carcinogenesis. Despite the therapeutic potential, there is currently no optimal approach for elevating the colonic microbiome's synthesis of SCFAs. In this study, poly(D,l-lactide-co-glycolide) (PLGA) was investigated for this application, as it was hypothesised that the colonic microbiota would metabolise PLGA to its lactate monomers, which would promote the resident microbiota's synthesis of SCFAs. Two grades of spray dried PLGA, alongside a lactate bolus control, were screened in an advanced model of the human colon, known as the M-SHIME® system. Whilst the high molecular weight (Mw) grade of PLGA was stable in the presence of the microbiota sourced from three healthy humans, the low Mw PLGA (PLGA 2) was found to be metabolised. This microbial degradation led to sustained release of lactate over 48 h and increased concentrations of the SCFAs propionate and butyrate. Further, microbial synthesis of harmful ammonium was significantly reduced compared to untreated controls. Interestingly, both types of PLGA were found to influence the composition of the luminal and mucosal microbiota in a donor-specific manner. An in vitro model of an inflamed colonic epithelium also showed the polymer to affect the expression of pro- and anti-inflammatory markers, such as interleukins 8 and 10. The findings of this study reveal PLGA's sensitivity to enzymatic metabolism in the gut, which could be harnessed for therapeutic elevation of colonic SCFAs.

Evaluation of the antifungal properties of nanoliposomes containing rhinacanthin-C isolated from the leaves of Rhinacanthus nasutus.

Fungal infections represent a challenging threat to the human health. Microsporum gypseum and Trichophyton rubrum are pathogenic fungi causing various topical mycoses in humans. The globally emerging issue of resistance to fungi demands the development of novel therapeutic strategies. In this context, the application of nanoliposomes as vehicles for carrying active therapeutic agents can be a suitable alternative. In this study, rhinacanthin-C was isolated from Rhinacanthus naustus and encapsulated in nano-liposomal formulations, which were prepared by the modified ethanol injection method. The two best formulations composed of soybean phosphatidylcholine (SPC), cholesterol (CHL), and tween 80 (T80) in a molar ratio of 1:1:0 (F1) and 1:1:0.5 (F2) were proceeded for experimentation. The physical characteristics and antifungal activities were performed and compared with solutions of rhinacanthin-C. The rhinacanthin-C encapsulating efficiencies in F1 and F2 were 94.69 ± 1.20% and 84.94 ± 1.32%, respectively. The particle sizes were found to be about 221.4 ± 13.76 nm (F1) and 115.8 ± 23.33 nm (F2), and zeta potential values of -38.16 mV (F1) and -40.98 mV (F2). Similarly, the stability studies of rhinacanthin-C in liposomes demonstrated that rhinacanthin-C in both formulations was more stable in mediums with pH of 4.0 and 6.6 than pure rhinacanthin-C when stored at the same conditions. Rhinacanthin-C in F1 was slightly more stable than F2 when stored in mediums with a pH of 10.0 after three months of storage. However, rhinacanthin-C in both formulations was less stable than pure rhinacanthin-C in a basic medium of pH 10.0. The antifungal potential was evaluated against M. gypsum and T. rubrum. The findings revealed a comparatively higher zone of inhibition for F1. In the MIC study, SPC: CHL: T80 showed higher inhibition against M. gypseum and a slightly higher inhibition against T. rubrum compared to free rhinacanthin-C solution. Moreover, rhinacanthin-C showed significant interaction against 14α-demethylase in in silico study. Overall, this study demonstrates that nanoliposomes containing rhinacanthin-C can improve the stability and antifungal potential of rhinacanthin-C with sustained and prolonged duration of action and could be a promising vehicle for delivery of active ingredients for targeting various fungal infections.