Outcomes and Long-Term Survival of Adolescent and Young Adult Patients Admitted to the Intensive Care Unit Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience of 152 Patients.

BACKGROUND AND OBJECTIVES: Prognostic factors reliably predicting outcomes for critically ill adolescent and young adult (AYA) patients undergoing allogeneic hematopoietic cell transplantation (allo-HSCT) are lacking. We assessed transplant and intensive care unit (ICU)-related factors impacting patient outcomes. PATIENTS AND METHODS: AYA patients who underwent allo-HSCT and required ICU admission at a Tertiary care Centre, during the period of 2003-2013, were included in this retrospective review. This was a non-interventional study. Only outcomes after the first allo-HSCT and index ICU admissions were analyzed. Disease-, transplant-, and ICU-related variables were analyzed to identify risk factors predictive of survival. RESULTS: Overall, 152 patients were included (males, 60.5%); median age at transplantation was 24 years (interquartile range [IQR] 18-32.5); median age at admission to the ICU was 25.8 years (IQR 19-34). Eighty-four percent underwent transplantation for a hematological malignancy; 129 (85%) received myeloablative conditioning. Seventy-one percent of ICU admissions occurred within the first year after allo-HSCT. ICU admission was primarily due to respiratory failure (47.3%) and sepsis (43.4%). One hundred and three patients (68%) died within 28 days of ICU admission. The 1- and 5-year overall survival rates were 19% and 17%, respectively. Main causes for ICU-related death were refractory septic shock with multiorgan failure (n = 49, 32%) and acute respiratory distress syndrome (ARDS) (n = 39, 26%). Univariate analysis showed that ICU mortality was associated with an Acute Physiology and Chronic Health Evaluation (APACHE) II score >20, a sequential organ failure assessment (SOFA score) > 12, a high lactate level, anemia, thrombocytopenia, leukopenia, hyperbilirubinemia, a high international normalized ratio (INR) and acute graft-versus-host disease (GVHD). Multivariate analysis identified thrombocytopenia, high INR, and acute GVHD as independent predictors of mortality. CONCLUSIONS: In AYA allo-HSCT patients admitted to the ICU, mortality remains high. Higher SOFA and APACHE scores, the need for organ support, thrombocytopenia, coagulopathy, and acute GVHD predict poor outcomes.

Ibrexafungerp is efficacious in a neutropenic murine model of pulmonary mucormycosis as monotherapy and combined with liposomal amphotericin B.

Ibrexafungerp (formerly SCY-078) is the first member of the triterpenoid class that prevents the synthesis of the fungal cell wall polymer ß-(1,3)-D-glucan by inhibiting the enzyme glucan synthase. We evaluated the in vivo efficacy of ibrexafungerp against pulmonary mucormycosis using an established murine model. Neutropenic mice were intratracheally infected with either Rhizopus delemar or Mucor circinelloides. Treatment with placebo (diluent control), ibrexafungerp (30 mg/kg, PO BID), liposomal amphotericin B (LAMB 10 mg/kg IV QD), posaconazole (PSC 30 mg/kg PO QD), or a combination of ibrexafungerp plus LAMB or ibrexafungerp plus PSC began 16 h post-infection and continued for 7 days for ibrexafungerp or PSC and through day 4 for LAMB. Ibrexafungerp was as effective as LAMB or PSC in prolonging median survival (range: 15 days to >21 days) and enhancing overall survival (30%-65%) vs placebo (9 days and 0%; P < 0.001) in mice infected with R. delemar. Furthermore, median survival and overall percent survival resulting from the combination of ibrexafungerp plus LAMB were significantly greater compared to all monotherapies (P ≤ 0.03). Similar survival results were observed in mice infected with M. circinelloides. Monotherapies also reduce the lung and brain fungal burden by ~0.5-1.0log10 conidial equivalents (CE)/g of tissue vs placebo in mice infected with R. delemar (P < 0.05), while a combination of ibrexafungerp plus LAMB lowered the fungal burden by ~0.5-1.5log10 CE/g compared to placebo or any of the monotherapy groups (P < 0.03). These results are promising and warrant continued investigation of ibrexafungerp as a novel treatment option against mucormycosis.

Peak Slope Ratio of the Recruitment Curves Compared to Muscle Evoked Potentials to Optimize Standing Configurations with Percutaneous Epidural Stimulation after Spinal Cord Injury.

Background: Percutaneous spinal cord epidural stimulation (pSCES) has effectively restored varying levels of motor control in persons with motor complete spinal cord injury (SCI). Studying and standardizing the pSCES configurations may yield specific motor improvements. Previously, reliance on the amplitude of the SCES-evoked potentials (EPs) was used to determine the correct stimulation configurations. Methods: We, hereby, retrospectively examined the effects of wide and narrow-field configurations on establishing the motor recruitment curves of motor units of three different agonist-antagonist muscle groups. Magnetic resonance imaging was also used to individualize SCI participants (n = 4) according to their lesion characteristics. The slope of the recruitment curves using a six-degree polynomial function was calculated to derive the slope ratio for the agonist-antagonist muscle groups responsible for standing. Results: Axial damage ratios of the spinal cord ranged from 0.80 to 0.92, indicating at least some level of supraspinal connectivity for all participants. Despite the close range of these ratios, standing motor performance was enhanced using different stimulation configurations in the four persons with SCI. A slope ratio of ≥1 was considered for the recommended configurations necessary to achieve standing. The retrospectively identified configurations using the supine slope ratio of the recruitment curves of the motor units agreed with that visually inspected muscle EPs amplitude of the extensor relative to the flexor muscles in two of the four participants. Two participants managed to advance the selected configurations into independent standing performance after using tonic stimulation. The other two participants required different levels of assistance to attain standing performance. Conclusions: The findings suggest that the peak slope ratio of the muscle agonists-antagonists recruitment curves may potentially identify the pSCES configurations necessary to achieve standing in persons with SCI.

In vitro biological studies and computational prediction-based analyses of pyrazolo[1,5-a]pyrimidine derivatives.

There is a need for new pharmaceutical discoveries from bioactive nitrogenous derivatives due to the emergence of scourges, numerous pandemics, and diverse health problems. In this context, pyrazolo[1,5-a]pyrimidine derivatives 12a and 12b were synthesized and screened to evaluate their biological potentials in vitro as antioxidants, anti-diabetics, anti-Alzheimer's, anti-arthritics, and anti-cancer agents. Additionally, the computational pharmacokinetic and toxicity properties of the two pyrazolo[1,5-a]pyrimidines 12a and 12b were calculated and analyzed. The preliminary studies and results of this work represent the initial steps toward more advanced studies and define the bioactive chemical structure of pyrazolo[1,5-a]pyrimidine derivatives with the goal of exploring new drugs to address numerous health problems.

Production and bioprocessing of Taxol from Aspergillus niger, an endophyte of Encephalartos whitelockii, with a plausible biosynthetic stability: antiproliferative activity and cell cycle analysis.

The biosynthetic potency of Taxol by fungi raises their prospective to be a platform for commercial production of Taxol, nevertheless, the attenuation of its productivity with the fungal storage, is the challenge. Thus, screening for a novel fungal isolate inhabiting ethnopharmacological plants, with a plausible metabolic stability for Taxol production could be one of the most affordable approaches. Aspergillus niger OR414905.1, an endophyte of Encephalartos whitelockii, had the highest Taxol productivity (173.9 µg/L). The chemical identity of the purified Taxol was confirmed by HPLC, FTIR, and LC-MS/MS analyses, exhibiting the same molecular mass (854.5 m/z) and molecular fragmentation pattern of the authentic Taxol. The purified Taxol exhibited a potent antiproliferative activity against HepG-2, MCF-7 and Caco-2, with IC50 values 0.011, 0.016, and 0.067 µM, respectively, in addition to a significant activity against A. flavus, as a model of human fungal pathogen. The purified Taxol displayed a significant effect against the cellular migration of HepG-2 and MCF-7 cells, by ~ 52-59% after 72 h, compared to the control, confirming its interference with the cellular matrix formation. Furthermore, the purified Taxol exhibited a significant ability to prompt apoptosis in MCF-7 cells, by about 11-fold compared to control cells, suppressing their division at G2/M phase. Taxol productivity by A. niger has been optimized by the response surface methodology with Plackett-Burman Design and Central Composite Design, resulting in a remarkable ~ 1.6-fold increase (279.8 µg/L), over the control. The biological half-life time of Taxol productivity by A. niger was ~ 6 months of preservation at 4 â„ƒ, however, the Taxol yield by A. niger was partially restored in response to ethyl acetate extracts of E. whitelockii, ensuring the presence of plant-derived signals that triggers the cryptic Taxol encoding genes.

The 90% effective dose of intrathecal hyperbaric bupivacaine for Cesarean delivery under combined spinal-epidural anesthesia in parturients with super obesity: an up-down sequential allocation study.

PURPOSE: To determine the 90% effective dose (ED90) of intrathecal hyperbaric bupivacaine for Cesarean delivery under combined spinal-epidural anesthesia (CSE) in parturients with super obesity (body mass index [BMI] ≥ 50 kg·m-2). METHODS: We enrolled parturients with BMI ≥ 50 kg·m-2 with term, singleton vertex pregnancies undergoing elective Cesarean delivery under CSE. An independent statistician generated the 0.75% hyperbaric bupivacaine dosing regimen in increments of 0.75 mg using a biased-coin up-down sequential allocation technique. This was combined with 15 µg fentanyl, 150 µg morphine, and normal saline to a volume of 2.05 mL. The initial and maximum doses were 9.75 mg and 12 mg, respectively. Participants, clinical team, and outcome assessors were blinded to the dose. The primary outcome was block success, defined as T6 block to pinprick within ten minutes and no intraoperative analgesic supplementation within 90 min of spinal injection. We determined the ED90 using logistic regression. RESULTS: We enrolled 45 parturients and included 42 in the analysis. All doses achieved a T6 level within ten minutes, and the primary outcome occurred in 0/1 (0%) of the 9.75-mg doses, 2/3 (67%) of the 10.5-mg doses, 21/27 (78%) of the 11.25-mg doses, and 11/11 (100%) of the 12-mg doses. The ED90 of hyperbaric bupivacaine was 11.56 mg (95% confidence interval, 11.16 to 11.99). Four parturients (9.5%) had sensory level higher than T2, but none was symptomatic or required general anesthesia. CONCLUSION: The estimated ED90 of hyperbaric bupivacaine with fentanyl and morphine in parturients with super obesity undergoing Cesarean delivery under CSE was approximately 11.5 mg. STUDY REGISTRATION: ClinicalTrials.gov (NCT03781388); first submitted 18 December 2018.

RéSUMé: OBJECTIF: Notre objectif était de déterminer la dose efficace à 90 % (DE90) de bupivacaïne hyperbare intrathécale pour l'accouchement par césarienne sous péri-rachianesthésie combinée (PRC) chez les personnes parturientes atteintes de super obésité (indice de masse corporelle [IMC] ≥ 50 kg·m−2). MéTHODE: Nous avons recruté des personnes parturientes ayant un IMC ≥ 50 kg·m−2 présentant des grossesses uniques à terme, en présentation céphalique et bénéficiant d'un accouchement par césarienne programmée sous PRC. Un·e statisticien·ne indépendant·e a généré le schéma posologique de bupivacaïne hyperbare à 0,75 % par incréments de 0,75 mg à l'aide d'une technique d'allocation séquentielle en escalier. La bupivacaïne a été combinée à 15 µg de fentanyl, 150 µg de morphine et à une solution physiologique salée jusqu'à un volume de 2,05 mL. Les doses initiale et maximale étaient respectivement de 9,75 mg et 12 mg. Les participant·es, l'équipe clinique et les personnes évaluant les résultats n'avaient pas connaissance de la dose. Le critère d'évaluation principal était la réussite du bloc, définie comme un bloc à T6 à la piqûre dans les dix minutes et aucune supplémentation analgésique peropératoire dans les 90 minutes suivant l'injection rachidienne. Nous avons déterminé la DE90 à l'aide d'une méthode de régression logistique. RéSULTATS: Nous avons recruté 45 personnes parturientes et en avons inclus 42 dans l'analyse. Toutes les doses ont atteint le niveau T6 en dix minutes, et le critère d'évaluation principal a été obtenu pour 0/1 (0 %) des doses de 9,75 mg, 2/3 (67 %) des doses de 10,5 mg, 21/27 (78 %) des doses de 11,25 mg et 11/11 (100 %) des doses de 12 mg. La DE90 de bupivacaïne hyperbare était de 11,56 mg (intervalle de confiance à 95 %, 11,16 à 11,99). Quatre personnes parturientes (9,5 %) ont affiché un niveau sensoriel supérieur à T2, mais aucune n'était symptomatique ni n'a nécessité d'anesthésie générale. CONCLUSION: La DE90 estimée de bupivacaïne hyperbare avec fentanyl et morphine chez les personnes parturientes hyperobèses bénéficiant d'une césarienne sous PRC était d'environ 11,5 mg. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT03781388); soumis pour la première fois le 18 décembre 2018.

Synthesis, in silico ADMET prediction analysis, and pharmacological evaluation of sulfonamide derivatives tethered with pyrazole or pyridine as anti-diabetic and anti-Alzheimer's agents.

Based on previous developments of our research programs in trying to find new compounds with multiple biological targets such as antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic agents. In the context, a novel series of sulfonamide derivatives based on the pyrazole or pyridine moieties 3a, b, 7-9, 11-13, 15a, b, and 16 were synthesized from amine compounds with sulfonyl chloride derivatives. The structures of sulfonamide derivatives were elucidated via spectroscopy (1H and 13C NMR). The sulfonamide derivatives were biologically assessed in vitro for their anti-diabetic (α-amylase and α-glucosidase inhibition) and anti-Alzheimer's (acetylcholinesterase inhibition) activities. The biological results revealed that compound 15a is a powerful enzyme inhibitor for α-amylase and α-glucosidase. Also, compound 15b demonstrated inhibitor activity against the acetylcholinesterase enzyme. The structure-activity relationship study of sulfonamide derivatives was accomplished. Furthermore, complementary in silico molecular properties, drug-likeness, ADMET prediction, and surface properties of the two more powerful derivatives 15a and 15b were fulfilled and computed. These studies recommend 15a and 15b as candidates with modifications in their structures before the in vivo assays.

State of art of mobility medicine: some more abstracts and evidence that the success of Pdm3 is based on extra-session relationships.

Scientific conferences increasingly suffer from the need for short presentations in which speakers like to dwell on the details of their work. A mitigating factor is to encourage discussion and planning of collaborations by organizing small meetings in a hotel large enough to host all attendees. This extends discussions' opportunities during morning breakfasts, lunches, dinners and long evenings together. Even if the vast majority of participants will not stay for the entire duration of the Conference, the possibilities for specialists to interact with specialists who are even very distant in terms of knowledge increase enormously. In any case, the results in terms of new job opportunities for young participants outweigh the costs for the organizers. Thirty years of Padova Muscle Days offer many examples, but the authors of this report on the state of the art of Mobility Medicine testify that this also happened in the 2024 Five Days of Muscle and Mobility Medicine (2024Pdm3) hosted at the Hotel Petrarca, Thermae of Euganea Hills and Padua, Italy which is in fact a valid countermeasure to the inevitable tendencies towards hyperspecialization that the explosive increase in scientific progress brings with it.

Optimization of Potent Ligands for the E3 Ligase DCAF15 and Evaluation of Their Use in Heterobifunctional Degraders.

Unlocking novel E3 ligases for use in heterobifunctional PROTAC degraders is of high importance to the pharmaceutical industry. Over-reliance on the current suite of ligands used to recruit E3 ligases could limit the potential of their application. To address this, potent ligands for DCAF15 were optimized using cryo-EM supported, structure-based design to improve on micromolar starting points. A potent binder, compound 24, was identified and subsequently conjugated into PROTACs against multiple targets. Following attempts on degrading a number of proteins using DCAF15 recruiting PROTACs, only degradation of BRD4 was observed. Deconvolution of the mechanism of action showed that this degradation was not mediated by DCAF15, thereby highlighting both the challenges faced when trying to expand the toolbox of validated E3 ligase ligands for use in PROTAC degraders and the pitfalls of using BRD4 as a model substrate.

Expression of concern: Effectiveness of some novel heterocyclic compounds as corrosion inhibitors for carbon steel in 1 M HCl using practical and theoretical methods.

Expression of concern for 'Effectiveness of some novel heterocyclic compounds as corrosion inhibitors for carbon steel in 1 M HCl using practical and theoretical methods' by Abd El-Aziz S. Fouda et al., RSC Adv., 2021, 11, 19294-19309, https://doi.org/10.1039/D1RA03083C.

Expression of concern: Experimental and surface morphological studies of corrosion inhibition on carbon steel in HCl solution using some new hydrazide derivatives.

Expression of concern for 'Experimental and surface morphological studies of corrosion inhibition on carbon steel in HCl solution using some new hydrazide derivatives' by Abd El-Aziz S. Fouda et al., RSC Adv., 2021, 11, 13497-13512, https://doi.org/10.1039/d1ra01405f.

Expression of concern: Impact of some pyrrolidinium ionic liquids on copper dissolution behavior in acidic environment: experimental, morphological and theoretical insights.

Expression of concern for 'Impact of some pyrrolidinium ionic liquids on copper dissolution behavior in acidic environment: experimental, morphological and theoretical insights' by Emad E. El-Katori and Ashraf S. Abousalem, RSC Adv., 2019, 9, 20760-20777, https://doi.org/10.1039/C9RA03603B.

Cognitive and Cerebrospinal Fluid Alzheimer's Disease-related Biomarker Trajectories in Older Surgical Patients and Matched Nonsurgical Controls.

BACKGROUND: Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults. METHODS: The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid ß (Aß) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls. RESULTS: The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aß, tau, or p-tau levels, or tau/Aß or p-tau/Aß ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 [95% CI, -0.06 to 0.43]; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (ß, -0.31 [95% CI, -0.45 to -0.17]; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up. CONCLUSIONS: During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aß) changes or greater cognitive decline.

The International Functional Electrical Stimulation Society (IFESS): Highlights from the IFESS conference at Rehabweek 2023.

The annual conference of the International Functional Electrical Stimulation Society (IFESS) was held in conjunction with the 7th RehabWeek Congress, from September 24 to 28, 2023 at the Resorts World Convention Centre on Sentosa Island, in Singapore. The Congress was a joint meeting of the International Consortium on Rehabilitation Technology (ICRT) together with 10 other societies in the field of assistive technology and rehabilitation engineering. The conference features comprehensive blend of technical and clinical context of FES, a sustained value the society has offered over many years. The cross- and inter- disciplinary approach of medicine, engineering, and science practiced in the FES community had enabled vibrant interaction, creation, and development of impactful and novel contributions to the field of FES, translating FES directly into highly relevant and sustainable solutions for the users.

Hydrogen bond-mediated self-assembly of Tin (II) oxide wrapped with Chitosan/[BzPy]Cl network: An effective bionanocomposite for textile wastewater remediation.

A novel and efficient bionanocomposite was synthesized by incorporating SnO into chitosan (Ch) and a room-temperature ionic liquid (RTIL). The bionanocomposite was synthesized in benzoyl pyridinium chloride [BzPy]Cl to maintain the unique properties of SnO, chitosan, and the ionic liquid. Adsorption and photodegradation processes were applied to evaluate the bionanocomposite for removing azo and anthraquinone dyes and textile wastewater. SnO/[BzPy]Cl and SnO/[BzPy]Cl/Ch samples were prepared and characterized using various techniques, including FT-IR, SEM, XRD, EDAX, XPS, DSC, TGA, nitrogen adsorption/desorption isotherm, and DRS analysis. SEM analysis revealed a hierarchical roughened rose flower-like morphology for the biocomposite. The band gap energies of SnO/[BzPy]Cl and SnO/[BzPy]Cl/chitosan were found to be 3.9 and 3.3 eV, respectively, indicating a reduction in the band gap energy with the introduction of [BzPy]Cl and chitosan. SnO/[BzPy]Cl/Ch showed high removal rates (92-95 %) for Fast Red, Blue 15, Red 120, Blue 94, Yellow 160, and Acid Orange 7 dyes. The adsorption kinetics followed a pseudo-second-order model. In addition, the effect of different photodegradation parameters such as solution pH, dye concentrations, contact time, and amount of photocatalyst, was studied. Given the optimal results obtained in removing azo and anthraquinone dyes, the SnO/[BzPy]Cl/Ch nanocomposite was used as an efficient nanocomposite for removing dyes from textile wastewater. The highest removal efficiency was found to be 95.8 %, obtained under ultraviolet and visible light. Furthermore, BOD and COD reduction analysis showed significant reductions, indicating the excellent performance of the photocatalyst.

The Association of Guideline-Directed Prophylaxis With Postoperative Nausea and Vomiting in Adult Patients: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Consensus guidelines for postoperative nausea and vomiting (PONV) prophylaxis recommend a risk-based approach in which the number of antiemetics administered is based on a preoperative estimate of PONV risk. These guidelines have been adapted by the Multicenter Perioperative Outcomes Group (MPOG) to serve as measures of clinician and hospital compliance with guideline-recommended care. However, the impact of this approach on clinical outcomes is not known. METHODS: We performed a single-center, retrospective study of adult patients undergoing general anesthesia from 2018 to 2021. Risk factors for PONV were defined using MPOG definitions: female sex, history of PONV or motion sickness, nonsmoker, inhaled anesthesia >60 minutes, high-risk procedure (cholecystectomy, laparoscopic, gynecologic), and age <50 years. Adequate prophylaxis was defined using the MPOG PONV-05 metric: at least 2 agents for patients with 1 to 2 risk factors and at least 3 agents for patients with 3+ risk factors. PONV was defined as documented PONV or receipt of rescue antiemetics. To estimate the association between adequate prophylaxis and PONV, we used Bayesian binomial models with overlap propensity score weighting. RESULTS: We included 76,703 cases (43% receiving adequate prophylaxis) with PONV occurring in 19%. In unadjusted and unweighted comparison, adequate prophylaxis was associated with increased incidence of PONV: median odds ratio 1.21 (95% credible interval [1.16-1.25]). However, after propensity score weighting and multivariable adjustment, adequate prophylaxis was associated with reduced relative and absolute risk for PONV: weighted marginal median odds ratio 0.90 [0.84-0.98] and absolute risk reduction (ARR) 1.6% [0.6%-2.6%]. There was evidence for a differential effect of adequate prophylaxis across the guideline-defined risk spectrum, with benefit seen in patients with 1 to 5 risk factors (conditional probabilities of benefit >0.81), but not in those at high predicted risk. Patient-specific, covariate-adjusted ARR was heterogeneous, with a median patient-specific conditional probability of benefit of 0.84 (95% credible interval, 0.73-0.90). CONCLUSIONS: Guideline-directed PONV prophylaxis is associated with a modest reduction in PONV, although this effect is small and heterogeneous on the absolute scale. We found evidence for a differential association between adequate prophylaxis and PONV across the guideline-defined risk spectrum, with diminution in patients at very high predicted preoperative risk. While patient-specific benefit was heterogenous, most patients had reasonably high predicted probabilities of absolute benefit from a guideline-directed strategy. Further assessment of these associations in a multicenter setting, with more robust investigation of risk prediction methods will allow for better understanding of the optimal approach to PONV prophylaxis.

Bioprocessing of Epothilone B from Aspergillus fumigatus under solid state fermentation: Antiproliferative activity, tubulin polymerization and cell cycle analysis.

Epothilone derivatives have been recognized as one of the most powerful anticancer drugs towards solid tumors, for their unique affinity to bind with ß-tubulin microtubule arrays, stabilizing their disassembly, causing cell death. Sornagium cellulosum is the main source for Epothilone, however, the fermentation bioprocessing of this myxobacteria is the main challenge for commercial production of Epothilone. The metabolic biosynthetic potency of epothilone by Aspergillus fumigatus, an endophyte of Catharanthus roseus, raises the hope for commercial epothilone production, for their fast growth rate and feasibility of manipulating their secondary metabolites. Thus, nutritional optimization of A. fumigatus for maximizing their epothilone productivity under solid state fermentation process is the objective. The highest yield of epothilone was obtained by growing A. fumigatus on orange peels under solid state fermentation (2.2 µg/g), bioprocessed by the Plackett-Burman design. The chemical structure of the extracted epothilone was resolved from the HPLC and LC-MS/MS analysis, with molecular mass 507.2 m/z and identical molecular fragmentation pattern of epothilone B of S. cellulosum. The purified A. fumigatus epothilone had a significant activity towards HepG2 (IC50 0.98 µg/ml), Pancl (IC50 1.5 µg/ml), MCF7 (IC50 3.7 µg/ml) and WI38 (IC50 4.6 µg/ml), as well as a strong anti-tubulin polymerization activity (IC50 0.52 µg/ml) compared to Paclitaxel (2.0 µg/ml). The effect of A. fumigatus epothilone on the immigration ability of HepG2 cells was assessed, as revealed from the wound closure of the monolayer cells that was estimated by ~ 63.7 and 72.5%, in response to the sample and doxorubicin, respectively, compared to negative control. From the Annexin V-PI flow cytometry results, a significant shift of the normal cells to the apoptosis was observed in response to A. fumigatus epothilone by ~ 20 folds compared to control cells, with the highest growth arrest of the HepG2 cells at the G0-G1 stage.

Camptothecin bioprocessing from Aspergillus terreus, an endophyte of Catharanthus roseus: antiproliferative activity, topoisomerase inhibition and cell cycle analysis.

Attenuation of camptothecin (CPT) productivity by fungi with preservation and subculturing is the challenge that halts fungi to be an industrial platform of CPT production. Thus, screening for novel endophytic fungal isolates with metabolic stability for CPT production was the objective. Catharanthus roseus is one of the medicinal plants with diverse bioactive metabolites that could have a plethora of novel endophytes with unique metabolites. Among the endophytes of C. roseus, Aspergillus terreus EFBL-NV OR131583.1 had the most CPT producing potency (90.2 µg/l), the chemical identity of the putative CPT was verified by HPLC, FT-IR, NMR and LC-MS/MS. The putative A. terreus CPT had the same molecular mass (349 m/z), and molecular fragmentation patterns of the authentic one, as revealed from the MS/MS analyses. The purified CPT had a strong activity against MCF7 (5.27 µM) and UO-31 (2.2 µM), with a potential inhibition to Topo II (IC50 value 0.52 nM) than Topo 1 (IC50 value 6.9 nM). The CPT displayed a high wound healing activity to UO-31 cells, stopping their metastasis, matrix formation and cell immigration. The purified CPT had a potential inducing activity to the cellular apoptosis of UO-31 by ~ 17 folds, as well as, arresting their cellular division at the S-phase, compared to the control cells. Upon Plackett-Burman design, the yield of CPT by A. terreus was increased by ~ 2.6 folds, compared to control. The yield of CPT by A. terreus was sequentially suppressed with the fungal storage and subculturing, losing ~ 50% of their CPT productivity by 3rd month and 5th generation. However, the productivity of the attenuated A. terreus culture was completely restored by adding 1% surface sterilized leaves of C. roseus, and the CPT yield was increased over-the-first culture by ~ 3.2 folds (315.2 µg/l). The restoring of CPT productivity of A. terreus in response to indigenous microbiome of C. roseus, ensures the A. terreus-microbiome interactions, releasing a chemical signal that triggers the CPT productivity of A. terreus. This is the first reports exploring the potency of A. terreus, endophyte of C. roseus" to be a platform for industrial production of CPT, with an affordable sustainability with addition of C. roseus microbiome.

Investigating the effect of changing the substrate material analyzed by laser-induced breakdown spectroscopy on the antenna performance.

Miniaturized microstrip antennas are efficiently utilized in MICS band wearable and implantable medical applications. However, the properties of the materials employed for antenna fabrication influence its resultant parameters and play a vital role in its performance. Rogers have been widely used as a substrate material in various antenna designs. In this work, a proof of concept study has been conducted to determine how altering the substrate used in antenna construction affects antenna performance. Using the laser-induced breakdown spectroscopy (LIBS) approach, the elements present in the two distinct substrate raw materials were compared to investigate potential effects on the antenna's performance. Given their accessibility and widespread use, two types of Rogers' substrates, RO 3210 and RO 4003, were selected. Furthermore, two identical antenna designs were modeled and fabricated using the two substrate materials. The reflection coefficient (S11) and other antenna parameters were determined and compared. Moreover, the recorded LIBS spectra were evaluated using principle component analysis and partial least square regression techniques. The LIBS spectra showed different copper and iron contents between the two Rogers (i.e., other dielectric properties), leading to a frequency shift. Additionally, impurities in the fabricated material increase the possible losses. Consequently, the elemental contents of the utilized Rogers control the antenna's performance and can ensure its safety in wearable and implant applications.