pH-Sensitive nanoparticles containing 5-fluorouracil and leucovorin as an improved anti-cancer option for colon cancer

Parenteral administration of chemotherapeutic drugs, 5-fluorouracil (5-FU) and leucovorin (LV), is commonly used to treat large bowel carcinomas such as colon cancer (CC) and colorectal carcinoma (CRC). Our study aims to design a novel nanoparticulate drug-delivery vehicle for oral use capable of colon-specific release. A modified double-emulsion solvent evaporation method was used in the preparation of pH-responsive Eudargit S100 polymeric nanoparticles, loaded with 5-FU/LV combination (5-FU/LV-loaded Eudargit S100 NPs). Our optimized drug-loaded NP showed a pH-responsive drug release and exhibited significantly more cytotoxic actions in cancer-cell lines than free drugs. These findings open the way for conducting clinical trials for colon malignancies treated with nanoparticles

pH-sensitive nanoparticles containing 5-fluorouracil and leucovorin as an improved anti-cancer option for colon cancer.

Parenteral administration of chemotherapeutic drugs, 5-fluorouracil (5-FU) and leucovorin (LV), is commonly used to treat large bowel carcinomas such as colon cancer (CC) and colorectal carcinoma (CRC). Our study aims to design a novel nanoparticulate drug-delivery vehicle for oral use capable of colon-specific release. A modified double-emulsion solvent evaporation method was used in the preparation of pH-responsive Eudargit S100 polymeric nanoparticles, loaded with 5-FU/LV combination (5-FU/LV-loaded Eudargit S100 NPs). Our optimized drug-loaded NP showed a pH-responsive drug release and exhibited significantly more cytotoxic actions in cancer-cell lines than free drugs. These findings open the way for conducting clinical trials for colon malignancies treated with nanoparticles

Relativistic Compact Objects in Isotropic Coordinates

We present a matrix method for obtaining new classes of exact solutions for Einstein's equations representing static perfect fluid spheres. By means of a matrix transformation, we reduce Einstein's equations to two independent Riccati type differential equations for which three classes of solutions are obtained. One class of the solutions corresponding to the linear barotropic type fluid with an equation of state $p=\gamma \rho$ is discussed in detail.Comment: 9 pages, no figures, accepted for publication in Pramana-Journal of Physic

Levi-Civita Solutions Coupled with Electromagnetic Fields

The local and global properties of the Levi-Civita (LC) solutions coupled with an electromagnetic field are studied and some limits to the vacuum LC solutions are given. By doing such limits, the physical and geometrical interpretations of the free parameters involved in the solutions are made clear. Sources for both the LC vacuum solutions and the LC solutions coupled with an electromagnetic field are studied, and in particular it is found that all the LC vacuum solutions with $\sigma \ge 0$ can be produced by cylindrically symmetric thin shells that satisfy all the energy conditions, weak, dominant, and strong. When the electromagnetic field is present, the situation changes dramatically. In the case of a purely magnetic field, all the solutions with $\sigma \ge 1/\sqrt{8}$ or $\sigma \le - 1/\sqrt{8}$ can be produced by physically acceptable cylindrical thin shells, while in the case of a purely electric field, no such shells are found for any value of $\sigma$.Comment: Typed in Revtex, including two figure

Bacterial Distribution in the Rhizosphere of Wild Barley under Contrasting Microclimates

Background: All plants in nature harbor a diverse community of rhizosphere bacteria which can affect the plant growth. Our samples are isolated from the rhizosphere of wild barley Hordeum spontaneum at the Evolution Canyon (‘EC’), Israel. The bacteria which have been living in close relationship with the plant root under the stressful conditions over millennia are likely to have developed strategies to alleviate plant stress. Methodology/Principal Findings: We studied distribution of culturable bacteria in the rhizosphere of H. spontaneum and characterized the bacterial 1-aminocyclopropane-1-carboxylate deaminase (ACCd) production, biofilm production, phosphorus solubilization and halophilic behavior. We have shown that the H. spontaneum rhizosphere at the stressful South Facing Slope (SFS) harbors significantly higher population of ACCd producing biofilm forming phosphorus solubilizing osmotic stress tolerant bacteria. Conclusions/Significance: The long-lived natural laboratory ‘EC ’ facilitates the generation of theoretical testable and predictable models of biodiversity and genome evolution on the area of plant microbe interactions. It is likely that the bacteria isolated at the stressful SFS offer new opportunities for the biotechnological applications in our agro-ecologica

Repurposing the oncolytic virus VSV∆51M as a COVID-19 vaccine

The coronavirus disease 2019 (COVID-19) pandemic imposes an urgent and continued need for the development of safe and cost-effective vaccines to induce preventive responses for limiting major outbreaks around the world. To combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we repurposed the VSV∆51M oncolytic virus platform to express the spike receptor-binding domain (RBD) antigen. In this study, we report the development and characterization of the VSV∆51M-RBD vaccine. Our findings demonstrate successful expression of the RBD gene by the VSV∆51M-RBD virus, inducing anti-RBD responses without attenuating the virus. Moreover, the VSV∆51M-RBD vaccine exhibited safety, immunogenicity, and the potential to serve as a safe and effective alternative or complementary platform to current COVID-19 vaccines

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely