Designs of clinical swallowability assessments of solid oral dosage forms in regulatory submissions.

The swallowability of solid oral dosage forms (SODFs) is crucial for medication safety and adherence. Both regulatory agencies and sponsors are concerned with bringing swallowable SODFs to patients. However, no best practices are available for assessing swallowability. Therefore, we conducted a comparative analysis of clinical swallowability assessments (CSAs) for SODFs in regulatory submissions to identify current study design practices. CSAs were identified from a "swallowability" keyword search of a Food and Drug Administration database. Notable design trends among the 17 CSAs were not assessing swallowability as a primary endpoint (76 %); enrolling pediatric patients (76 %); administering assessments post-screening (76 %); and utilizing questionnaires (100 %). A design trend with near equal frequency (∼50 %) was single- or multiple-doses of product administration. Study subjects were the primary questionnaire respondents (82 %), usually using a Likert scale (92 %, 12/13). CSAs generally dichotomized the responses for analysis (65 %) without pre-specified threshold values (59 %). Overall, while study designs exhibited trends, methodology variations may impact swallowability measurements affecting the interpretation of results. Thus, developing robust and valid assessment tools for swallowability is imperative to produce clinically relevant data and inform regulatory decision-making. Collaboration between regulatory agencies and sponsors is warranted to create best practices and ensure high quality swallowability data.

Enzyme-assisted high throughput sequencing of an expanded genetic alphabet at single base resolution.

With just four building blocks, low sequence information density, few functional groups, poor control over folding, and difficulties in forming compact folds, natural DNA and RNA have been disappointing platforms from which to evolve receptors, ligands, and catalysts. Accordingly, synthetic biology has created "artificially expanded genetic information systems" (AEGIS) to add nucleotides, functionality, and information density. With the expected improvements seen in AegisBodies and AegisZymes, the task for synthetic biologists shifts to developing for expanded DNA the same analytical tools available to natural DNA. Here we report one of these, an enzyme-assisted sequencing of expanded genetic alphabet (ESEGA) method to sequence six-letter AEGIS DNA. We show how ESEGA analyses this DNA at single base resolution, and applies it to optimized conditions for six-nucleotide PCR, assessing the fidelity of various DNA polymerases, and extending this to AEGIS components with functional groups. This supports the renewed exploitation of expanded DNA alphabets in biotechnology.

Development of the multiplex imaging chamber at PAL-XFEL.

Various X-ray techniques are employed to investigate specimens in diverse fields. Generally, scattering and absorption/emission processes occur due to the interaction of X-rays with matter. The output signals from these processes contain structural information and the electronic structure of specimens, respectively. The combination of complementary X-ray techniques improves the understanding of complex systems holistically. In this context, we introduce a multiplex imaging instrument that can collect small-/wide-angle X-ray diffraction and X-ray emission spectra simultaneously to investigate morphological information with nanoscale resolution, crystal arrangement at the atomic scale and the electronic structure of specimens.

The feasibility of MR elastography with transpelvic vibration for localization of focal prostate lesion.

We aimed to evaluate the feasibility of MR elastography (MRE) using a transpelvic approach. Thirty-one patients who underwent prostate MRE and had a pathological diagnosis were included in this study. MRE was obtained using a passive driver placed at the umbilicus and iliac crests. The shear stiffness, clinical data, and conventional imaging findings of prostate cancer and benign prostatic hyperplasia (BPH) were compared. Inter-reader agreements were evaluated using the intraclass coefficient class (ICC). Prostate MRE was successfully performed for all patients (100% technical success rate). Nineteen cancer and 10 BPH lesions were visualized on MRE. The mean shear stiffness of cancer was significantly higher than that of BPH (5.99 ± 1.46 kPa vs. 4.67 ± 1.54 kPa, p = 0.045). One cancer was detected on MRE but not on conventional sequences. Six tiny cancer lesions were not visualized on MRE. The mean size of cancers that were not detected on MRE was smaller than that of cancers that were visible on MRE (0.8 ± 0.3 cm vs. 2.3 ± 1.8 cm, p = 0.001). The inter-reader agreement for interpreting MRE was excellent (ICC = 0.95). Prostate MRE with transpelvic vibration is feasible without intracavitary actuators. Transpelvic prostate MRE is reliable for detecting focal lesions, including clinically significant prostate cancer and BPH.

The effect of different LED wavelengths on the components and biosynthesis of isoflavonoid in sprout Astragalus membranaceus.

An artificial light source is the optimal element for studying the usability of the medicinal plant Astragalus membranaceus as a sprout vegetable. Based on artificial light source conditions, formononetin (FO) level was the highest (2.6 mg/L) in A. membranaceus exposed to white light emitting diode (LED) light, and calycosin (CA) level was the highest (3.09 mg/L) in the plant exposed to red LED light. According to the publicly available transcriptome data of LED-exposed sprout A. membranaceus LED, reference genes related to the content enhancement of FO, an isoflavone compound, and those related to the content enhancement of CA were selected. The expression patterns of these genes were assayed using qPCR. Among the genes related to FO enhancement, Gene-225190T showed the highest mRNA levels in cells of LED-white light-exposed sprout A. membranaceus; among the genes related to CA enhancement, Gene_042770T showed the highest expression under red LED light. Most genes related to the overall biosynthesis regulation of flavonoids of the upper concept of isoflavone were highly expressed in response to red LED light, and the transcriptional level of 4CL in response to red LED light was the highest. Based on these results, the artificial light sources that regulated the FO and CA contents in sprouts A. membranaceus were white and red LED lights, and the selected reference genes were capable of regulating isoflavone biosynthesis.

Use of physiologically-based pharmacokinetic modeling to understand the effect of omeprazole administration on the pharmacokinetics of oral extended-release nifedipine.

Proton pump inhibitors (PPIs) can affect the release of drugs from their dosage forms in vivo by elevating the gastric pH. Our recent clinical study has demonstrated that drug-drug interactions (DDIs) exist between a PPI, omeprazole, and nifedipine extended-release formulations, where systemic exposure of nifedipine was increased in subjects after multiple-dose pretreatment of omeprazole. However, the mechanism of the observed DDIs between omeprazole and nifedipine has not been well-understood, as the DDI may also be mediated through CYP3A4 enzyme inhibition in addition to the elevated gastric pH caused by omeprazole. This study used physiologically-based pharmacokinetic (PBPK) modeling and simulations to investigate the underlying mechanism of these complex DDIs. A formulation exhibiting differences in in vitro dissolution across physiological pH range and another formulation where pH does not impact dissolution appreciably (e.g., an osmotic pump) were chosen to characterize the potential impact of pH. The PBPK models incorporated two-stage in vitro release profiles via US Pharmacopeia 2 apparatus. PBPK simulations suggest that the elevated gastric pH following multiple-dose administration of omeprazole has a minimal effect on nifedipine pharmacokinetics (PKs), whereas CYP3A4-mediated DDI is likely the main driver to the observed change of nifedipine PKs in the presence of omeprazole. Compared to the osmotic formulation, the slightly increased exposure of nifedipine can be accounted for by the enhanced drug release in the pH-dependent formulation. The reported model-based approach may be useful in DDI risk assessments, product formulation designs, and bioequivalence evaluations.

Antioxidant and Antiproliferative Activities of Eclipta prostrata (L.) L. Extract and Isolated Compounds.

The primary objective of this study was to elucidate the chemical composition, antioxidant properties, and antiproliferative activities of Eclipta prostrata extracts. Two flavonoids, 3'-O-methylorobol and apigenin 7-sulfate, were isolated from the ethyl acetate (EtOAc) extract of E. prostrata. The total phenolic and flavonoid contents of the E. prostrata extracts, as well as their overall antioxidant activities as measured using the 2,2-diphenyl-1-picrylhydrazyl and reducing power assays, were investigated. The E. prostrata EtOAc extract exhibited significantly greater antioxidant activities in both assays and higher phenol and flavonoid contents than the other extracts. The potential antiproliferative properties of the E. prostrata extracts and isolated compounds were investigated in vitro against the AGS, A549, and HT-29 cancer cell lines and the normal human HEK-293 cell line using the MTT assay. Annexin V-FITC/PI staining analysis and quantitative real-time PCR were used to assess AGS cell apoptosis. At a concentration of 100 µg/mL, the EtOAc extract of E. prostrata reduced AGS cell viability and proliferation by inducing apoptosis through the alteration of gene expression in the apoptotic cascade. These results highlight E. prostrata as a promising source of anticancer compounds.

Unusual grafts for living-donor liver transplantation.

PURPOSE: Unusual grafts, including extended left liver plus caudate lobe, right anterior section, and right posterior section grafts, are alternatives to left and right lobe grafts for living-donor liver transplantation. This study aimed to investigate unusual grafts from the perspectives of recipients and donors. METHODS: From 2016 to 2021, 497 patients received living-donor liver transplantation at Severance Hospital. Among them, 10 patients received unusual grafts. Three patients received extended left liver plus caudate lobe grafts, two patients received right anterior section grafts, and five patients received right posterior section grafts. Liver volumetrics and anatomy were analyzed for all recipients and donors. We collected data on laboratory examinations (alanine aminotransferase, total bilirubin, international normalized ratio), imaging studies, graft survival, and complications. A 1:2 ratio propensity-score matching method was used to reduce selection bias and balance variables between the unusual and conventional graft groups. RESULTS: The median of Model for End-stage Liver Disease score of unusual graft recipients was 13.5 (interquartile range 11.5-19.3) and that of graft-recipient weight ratio was 0.767 (0.7-0.9). ABO incompatibility was observed in four cases. The alanine aminotransferase level, total bilirubin level, and international normalized ratio decreased in both recipients and donors. Unusual and conventional grafts had similar survival rates (p = 0.492). The right and left subgroups did not differ from each counter-conventional subgroup (p = 0.339 and p = 0.695, respectively). The incidence of major complications was not significantly different between unusual and conventional graft recipients (p = 0.513). Wound seromas were reported by unusual graft donors; the complication ratio was similar to that in conventional graft donors (p = 0.169). CONCLUSION: Although unusual grafts require a complex indication, they may show feasible surgical outcomes for recipients with an acceptable donor complication.

Enzymatic synthesis and nanopore sequencing of 12-letter supernumerary DNA.

The 4-letter DNA alphabet (A, T, G, C) as found in Nature is an elegant, yet non-exhaustive solution to the problem of storage, transfer, and evolution of biological information. Here, we report on strategies for both writing and reading DNA with expanded alphabets composed of up to 12 letters (A, T, G, C, B, S, P, Z, X, K, J, V). For writing, we devise an enzymatic strategy for inserting a singular, orthogonal xenonucleic acid (XNA) base pair into standard DNA sequences using 2'-deoxy-xenonucleoside triphosphates as substrates. Integrating this strategy with combinatorial oligos generated on a chip, we construct libraries containing single XNA bases for parameterizing kmer basecalling models for commercially available nanopore sequencing. These elementary steps are combined to synthesize and sequence DNA containing 12 letters - the upper limit of what is accessible within the electroneutral, canonical base pairing framework. By introducing low-barrier synthesis and sequencing strategies, this work overcomes previous obstacles paving the way for making expanded alphabets widely accessible.

Effect of the Similarity of Formulations and Excipients of Approved Generic Drug Products on In Vivo Bioequivalence for Putative Biopharmaceutics Classification System Class III Drugs.

One of the potential essential factors that restricts generic industry from applying the Biopharmaceutics Classification System (BCS) Class III biowaiver is adherence to the stringent formulation criteria for formulation qualitative (Q1) sameness and quantitative (Q2) similarity. The present study has investigated formulations and excipients from 16 putative BCS Class III drug substances in a total of 19 drug products via 133 approved abbreviated new drug applications (ANDAs) containing in vivo bioequivalence (BE) studies in human subjects during the time period from 2006 to 2022. We included the BCS Class III drugs in this study by referring to published literature, the World Health Organization (WHO) BCS Class I-IV list, FDA internal assessments, and physicochemical properties (high solubility and low permeability) of specific drug substances. Based upon all 133 approved generic formulations in this study, the highest amount of each different compendial excipient with a total of 40 is defined as its corresponding typical amount that has not shown any potential impact on in vivo drug absorption. In the present study, although only 30.08% of the investigated generic formulations met Q1 the same/Q2 similar formulation criteria for the BCS Class III biowaiver, and while approximately 69.92% failed to meet those criteria with non-Q1/Q2 similar formulations, all test/reference ratios (T/R) and 90% confidence intervals for all instrumental PK parameters (AUC0-t, AUC0-inf, and Cmax) met the bioequivalence (BE) criteria (80-125%). The results of formulation assessment suggest that the commonly used excipients without atypical amounts did not impact absorption of 16 putative BCS Class III drug substances. The rate and extent of absorption of drugs appears to be more dependent upon the biopharmaceutic and physiochemical properties of BCS Class III drug substance and less, or not dependent upon their formulations, excipients, and the excipients class. Our findings may lead to a more flexible formulation design space regarding the stringent BCS Class III formulation criteria.

Efficacy of Carbon Nanodots and Manganese Ferrite (MnFe2O4) Nanoparticles in Stimulating Growth and Antioxidant Activity in Drought-Stressed Maize Inbred Lines.

Despite being the third most-consumed crop, maize (Zea mays L.) is highly vulnerable to drought stress. The predominant secondary metabolite in plants is phenolic acids, which scavenge reactive oxygen species to minimize oxidative stress under drought stress. Herein, the effect of carbon nanodots (CND) and manganese ferrite (MnFe2O4) nanoparticles (NP) on the drought stress tolerance of maize has been studied. The experimental results revealed that the highest leaf blade length (54.0 cm) and width (3.9 cm), root length (45.2 cm), stem diameter (11.1 mm), root fresh weight (7.0 g), leaf relative water content (84.8%) and chlorogenic (8.7 µg/mL), caffeic (3.0 µg/mL) and syringic acid (1.0 µg/mL) contents were demonstrated by CND-treated (10 mg L-1) inbred lines (GP5, HW19, HCW2, 17YS6032, HCW3, HCW4, HW7, HCW2, and 16S8068-9, respectively). However, the highest shoot length (71.5 cm), leaf moisture content (83.9%), shoot fresh weight (12.5 g), chlorophyll content (47.3), and DPPH free radical scavenging activity (34.1%) were observed in MnFe2O4 NP-treated (300 mg L-1) HF12, HW15, 11BS8016-7, HW15, HW12, and KW7 lines, respectively. The results indicate that CND and MnFe2O4 NP can mitigate drought stress effects on different accessions of the given population, as corroborated by improvements in growth and physio-biochemical traits among several inbred lines of maize.

Effect of internet-based vs. in-person multimodal interventions on patients with mild to moderate Alzheimer's disease: a randomized, cross-over, open-label trial.

Objective: We aimed to investigate the effect of internet-based and in-person cognitive interventions on cognition, mood, and activities of daily living (ADL) on patients with mild to moderate Alzheimer's disease (AD) and examine whether internet-based intervention is as effective as the in-person intervention. Methods: We recruited 52 patients with probable mild AD, of whom 42 completed the trial. We randomly divided participants into intervention and control groups at a 1:1 ratio and statistically compared the neuropsychological test results of the two groups. In addition, patients in the intervention group were randomly assigned to a 4 weeks internet-based or in-person intervention, with subsequent crossover to the other group for 4 weeks. We statistically analyzed and compared the neuropsychological test scores between internet-based and in-person interventions. Results: Compared with the control group, the intervention group (internet-based and in-person) showed significantly improved profile in cognition (p < 0.001), depression (p < 0.001), anxiety (p < 0.001) and ADL (p < 0.001). In addition, the effect of the internet-based intervention on cognition (p = 0.918) and depression (p = 0.282) was not significantly different from that of the in-person intervention. However, in the Beck anxiety inventory (p = 0.009) and Seoul instrumental activity of daily living (p = 0.023), in-person intervention was more effective than internet-based intervention. Conclusion: This study suggests that both types of cognitive intervention (in-person and internet-based) may be viable supplementary treatments along with approved pharmacological therapy. In terms of anxiety and ADL, the effect of the in-person interventions may be more effective than the-internet based interventions.

CDC Bottle Bioassays for Detection of Insecticide Resistance in Culex Pipiens, Aedes Albopictus, and Aedes Koreicus Collected on US Army Garrisons, Republic of Korea.

Mosquito-borne pathogens are a threat to US troops stationed in the Republic of Korea (ROK). Insecticide resistance has been reported in mosquito vectors in the ROK, highlighting the need for a sustained ROK-wide resistance surveillance program. To address this need from April 2022 until October 2022, larvae and pupae of Aedes albopictus, Ae. koreicus, and Culex pipiens were collected from US Army Garrison (USAG) Daegu (Camps Carroll and Henry), USAG Yongsan-Casey (Camp Casey), and USAG Humphreys (Camp Humphreys) and screened for resistance to insecticides using the Centers for Disease Control and Prevention (CDC) bottle bioassay. No resistance to deltamethrin or chlorpyrifos was detected in Ae. albopictus populations, but one population showed possible resistance to permethrin. Aedes koreicus populations were found to be resistant to etofenprox and permethrin with possible resistance to deltamethrin but were susceptible to chlorpyrifos. Culex pipiens populations were found to be resistant to chlorpyrifos, permethrin, and deltamethrin. Screening using CDC bottle bioassays will continue, and efforts will be made to determine the operational impact of the assay results on military installation mosquito control programs.

Accurate Detection of Urothelial Bladder Cancer Using Targeted Deep Sequencing of Urine DNA.

Patients with hematuria are commonly given an invasive cystoscopy test to detect bladder cancer (BC). To avoid the risks associated with cystoscopy, several urine-based methods for BC detection have been developed, the most prominent of which is the deep sequencing of urine DNA. However, the current methods for urine-based BC detection have significant levels of false-positive signals. In this study, we report on uAL100, a method to precisely detect BC tumor DNA in the urine without tumor samples. Using urine samples from 43 patients with BC and 21 healthy donors, uAL100 detected BC with 83.7% sensitivity and 100% specificity. The mutations identified in the urine DNA by uAL100 for BC detection were highly associated with BC tumorigenesis and progression. We suggest that uAL100 has improved accuracy compared to other urine-based methods for early BC detection and can reduce unnecessary cystoscopy tests for patients with hematuria.

Synthetic Biology Pathway to Nucleoside Triphosphates for Expanded Genetic Alphabets.

One horizon in synthetic biology seeks alternative forms of DNA that store, transcribe, and support the evolution of biological information. Here, hydrogen bond donor and acceptor groups are rearranged within a Watson-Crick geometry to get 12 nucleotides that form 6 independently replicating pairs. Such artificially expanded genetic information systems (AEGIS) support Darwinian evolution in vitro. To move AEGIS into living cells, metabolic pathways are next required to make AEGIS triphosphates economically from their nucleosides, eliminating the need to feed these expensive compounds in growth media. We report that "polyphosphate kinases" can be recruited for such pathways, working with natural diphosphate kinases and engineered nucleoside kinases. This pathway in vitro makes AEGIS triphosphates, including third-generation triphosphates having improved ability to survive in living bacterial cells. In α-32P-labeled forms, produced here for the first time, they were used to study DNA polymerases, finding cases where third-generation AEGIS triphosphates perform better with natural enzymes than second-generation AEGIS triphosphates.

Cellular Morphology and Transcriptome Comparative Analysis of Astragalus membranaceus Bunge Sprouts Cultured In Vitro under Different LED Light.

Astragalus membranaceus, the major components of which are saponins, flavonoids, and polysaccharides, has been established to have excellent pharmacological activity. After ginseng, it is the second most used medicinal plant. To examine the utility of A. membranaceus as a sprout crop for plant factory cultivation, we sought to establish a functional substance control model by comparing the transcriptomes of sprouts grown in sterile, in vitro culture using LED light sources. Having sown the seeds of A. membranaceus, these were exposed to white LED light (continuous spectrum), red LED light (632 nm, 1.58 µmol/m2/s), or blue LED light (465 nm, 1.44 µmol/m2/s) and grown for 6 weeks; after which, the samples were collected for transcriptome analysis. Scanning electron microscopy analysis of cell morphology in plants exposed to the three light sources revealed that leaf cell size was largest in those plants exposed to red light, where the thickest stem was observed in plants exposed to white light. The total number of genes in A. membranaceus spouts determined via de novo assembly was 45,667. Analysis of differentially expressed genes revealed that for the comparisons of blue LED vs. red LED, blue LED vs. white LED, and red LED vs. white LED, the numbers of upregulated genes were 132, 148, and 144, respectively. Binding, DNA integration, transport, phosphorylation, DNA biosynthetic process, membrane, and plant-type secondary cell wall biogenesis were the most enriched in the comparative analysis of blue LED vs. red LED, whereas Binding, RNA-templated DNA biosynthetic process, DNA metabolic process, and DNA integration were the most enriched in the comparative analysis of blue vs. white LED, and DNA integration and resolution of meiotic recombination intermediates were the most enrichment in the comparison between red LED vs. white LED. The GO term associated with flavonoid biosynthesis, implying the functionality of A. membranaceus, was the flavonoid biosynthetic process, which was enriched in the white LED vs. red LED comparison. The findings of this study thus indicate that different LED light sources can differentially influence the transcriptome expression pattern of A. membranaceus sprouts, which can provide a basis for establishing a flavonoid biosynthesis regulation model and thus, the cultivation of high-functional Astragalus sprouts.

A process using a thermal reduction for producing the battery grade lithium hydroxide from wasted black powder generated by cathode active materials manufacturing.

Recent lithium consumption is doubled in a decade due to the Li-ion battery (LIB) demand for electric vehicles, the energy storage system, etc. The LIBs market capacity is expected to be in strong demand due to the political drive by many nations. Wasted black powders (WBP) are generated from the manufacturing of the cathode active material and spent LIBs. The recycling market capacity is also expected to expand rapidly. This study is to propose a thermal reduction technique for recovering Li selectively. The WBP, containing 7.4 % Li, 62.1 % Ni, 4.5 % Co, and 0.3 % Al, was reduced in a vertical tube furnace using a 10 % H2 gas as a reducing agent at 750 ºC for 1 h, and 94.3 % of Li was recovered from a water leaching, while other metal values, including Ni and Co remained in the residue. A leach solution was treated in a series of crystallisations, filtering, and washing. An intermediate product was produced and re-dissolved in hot water at 80 ºC for 0.5 h to minimise Li2CO3 content into a solution. A final solution was crystallised repeatedly to produce the final product. A 99.5 % of LiOH·H2O was characterised and passed the impurity specification by the manufacturer as a marketable product. The proposed process is relatively simple to utilise to scale up for bulk production, and it can also be contributed to the battery recycling industry as the spent LIBs are expected to overabundance within the near future. A brief cost evaluation confirms the process feasibility, particularly, for the company that produces cathode active material (CAM) and generates WBP in their own supply chain.

Clinical variation in the early assessment and management of suspected community-acquired meningitis: a multicentre retrospective study.

BACKGROUND: Bacterial meningitis is a medical emergency and timely management has been shown to improve outcomes. The aim of this study was to compare the early assessment and management of adults with suspected community-onset meningitis between hospitals and identify opportunities for clinical practice improvement. METHODS: This retrospective cohort study was conducted at three principal referral hospitals in Sydney, Australia. Adult patients with suspected meningitis undergoing cerebrospinal fluid sampling between 1 July 2018 and 31 June 2019 were included. Relevant clinical and laboratory data were extracted from the medical record. Differences between sites were analysed and factors associated with time to antimicrobial therapy were assessed by Cox regression. RESULTS: In 260 patients, the median time from triage to antibiotic administration was 332 min with a difference of up to 147 min between hospitals. Median time from triage to lumbar puncture (LP) was 366 min with an inter-hospital difference of up to 198 min. Seventy per cent of patients had neuroimaging prior to LP, and this group had a significantly longer median time to antibiotic administration (367 vs 231 min; P = 0.001). Guideline concordant antibiotics were administered in 84% of patients, with only 39% of those administered adjunctive corticosteroids. Seven (3%) patients had confirmed bacterial meningitis. Modifiable factors associated with earlier antimicrobial administration included infectious diseases involvement (adjusted hazard ratio [aHR], 1.50 [95% confidence interval (CI), 1.01-2.24]) and computed tomography (CT) scanning (aHR, 0.67 [95% CI, 0.46-0.98]). CONCLUSION: Opportunities for improvement include reducing the time to LP and antibiotic administration, improving coadministration of corticosteroids and avoiding potentially unnecessary CT scanning.

The effect of food vehicles on in vitro performance of pantoprazole sodium delayed release sprinkle formulation.

Certain patient populations, including children, the elderly or people with dysphagia, find swallowing whole medications such as tablets and capsules difficult. To facilitate oral administration of drugs in such patients, a common practice is to sprinkle the drug products (e.g., usually after crushing the tablet or opening the capsule) on food vehicles before consumption which improves swallowability. Thus, evaluation of the impact of food vehicles on the potency and stability of the administered drug product is important. The aim of the current study was to evaluate the physicochemical properties (viscosity, pH, and water content) of common food vehicles used for sprinkle administration (e.g., apple juice, applesauce, pudding, yogurt, and milk) and their impacts on the in vitro performance (i.e., dissolution) of pantoprazole sodium delayed release (DR) drug products. The food vehicles evaluated exhibited marked difference in viscosity, pH and water content. Notably, the pH of the food as well as the interaction between food vehicle pH and drug-food contact time were the most significant factors affecting the in vitro performance of pantoprazole sodium DR granules. For example, the dissolution of pantoprazole sodium DR granules sprinkled on food vehicles of low pH (e.g., apple juice or applesauce) for short durations remained unchanged compared with the control group (i.e., without mixing with food vehicles). However, use of high pH food vehicles (e.g., milk) with prolonged contact time (e.g., 2 h) resulted in accelerated pantoprazole release, drug degradation and loss of potency. Overall, a thorough assessment of physicochemical properties of food vehicles and formulation characteristics are a necessary part of the development of sprinkle formulations.

Technique and perioperative outcomes of single-port robotic surgery using the da Vinci SP platform in urology.

OBJECTIVE: To describe surgical technique for single port robotic surgery using the da Vinci SP system and report the perioperative outcomes. PATIENTS AND METHODS: Between Jan 2019 and Jan 2021, single-port robotic urologic surgeries were performed in 120 patients by a single surgeon. Clinicopathologic data and perioperative outcomes were collected. All surgical procedures were performed with a transperitoneal approach through an umbilical single port. Additional assistant port was used in complex procedures for malignant disease. Surgeries were carried out using both above and below camera position for effective retraction. For reconstructive surgery using intestine, an extra-intracorporeal hybrid method was used. Surgical procedures involving both kidney and pelvis were performed without change of patient position or trocar placement. RESULTS: Mean age was 62.7 years and 102 patients were male. For oncologic indication, 105 patients underwent surgeries including 66 radical prostatectomy, 25 partial nephrectomy, six radical nephrectomies, five nephroureterectomy and three radical cystectomy with urinary diversion. Fifteen cases with benign indication included four ureterolithotomy, seven uretero/pyeloplasty, three ureteroneocystostomy, and one ileal ureter reconstruction. All surgeries were performed successfully without conversion to other surgical approach. Clavien-Dindo grade III complication occurred in two patients. CONCLUSIONS: The da Vinci SP system provides a new robotic surgical platform for single port surgery while maintaining the major features of robotic surgery similar to multi-port surgery. Various single port urologic surgeries can be safely performed with this platform.