A 3-arm randomized control trial to compare the efficacy of re-circulant hyperthermic intravesical chemotherapy versus conventional intravesical mitomycin C and BCG therapy for intermediate-risk non-muscle invasive bladder cancer.

Introduction: To evaluate the efficacy and side effects of re-circulant hyperthermic intravesical chemotherapy versus conventional treatments for intermediate risk non-muscle invasive bladder cancer (NMIBC).

Methods: A randomized 3-arm, parallel group trial was conducted at a single tertiary care centre. 135 patients with low-grade intermediate-risk cancer, having undergone complete resection of bladder tumor were included.

Re-designing environmentally persistent pharmaceutical pollutant through programmed inactivation: The case of methotrexate.

Environmental emission of pharmaceutical pollutants notably causes the contamination of aquatic ecosystems and drinking water. Typically, reduction of these pollutants in the environment is mostly managed by ameliorated wastewater treatments. Here, we report a method for the eco-design of drugs through the introduction within the molecular structure of a sensitive chemical group responsive to water treatments.

Vinblastine loaded on graphene quantum dots and its anticancer applications.

Aims: The aim of our work is to load Vinblastine drugs loaded on graphene quantum dots to improve its cytotoxicity on cancer cells and reduce it on the normal cell in the composites. Moreover, the GQDs-Vin composite significantly inhibited tumour growth in animals.

Methods: GQDs-Vin composites were prepared by homogenisation of GQDs and Vin solutions.

Globally local: Hyper-local modeling for accurate forecast of COVID-19.

Importance: Assumption of a well-mixed population during modeling is often erroneously made without due analysis of its validity. Ignoring the importance of the geo-spatial granularity at which the data is collected could have significant implications on the quality of forecasts and the actionable clinical recommendations that are based on it.

Objective: This paper's primary objective is to test the hypothesis that the characteristic dynamics defining the trajectory of the pandemic in a region is lost when the data is aggregated and modeled at higher geo-spatial levels.

In-Cell Generation of Anticancer Phenanthridine Through Bioorthogonal Cyclization in Antitumor Prodrug Development.

Pharmacological inactivation of antitumor drugs toward healthy cells is a critical factor in prodrug development. Typically, pharmaceutical chemists graft temporary moieties to existing antitumor drugs to reduce their pharmacological activity. Here, we report a platform able to generate the cytotoxic agent by intramolecular cyclization.

Anticancer boron-containing prodrugs responsive to oxidative stress from the tumor microenvironment.

Boronic acid (and ester) prodrugs targeting the overexpressed level of reactive oxygen species within tumor microenvironment represent a promising area for the discovery of new selective anticancer chemotherapy. This strategy that emerged only ten years ago is exponentially growing and could demonstrate its clinical usefulness in the near future. Herein, the previously described small-molecule and macromolecular anticancer prodrugs activated by carbon-boron oxidation are gathered.

NMR Characterization of the Influence of Zinc(II) Ions on the Structural and Dynamic Behavior of the New Delhi Metallo-β-Lactamase-1 and on the Binding with Flavonols as Inhibitors.

New Delhi metallo-β-lactamase-1 (NDM-1) has recently emerged as a global threat because of its ability to confer resistance to all common β-lactam antibiotics. Understanding the molecular basis of β-lactam hydrolysis by NDM is crucial for designing NDM inhibitors or β-lactams resistant to their hydrolysis. In this study, for the first time, NMR was used to study the influence of Zn(II) ions on the dynamic behavior of NDM-1.

Use of Stratified Cascade Learning to predict hospitalization risk with only socioeconomic factors.

Background And Objective: Published models predicting health related outcomes rely on clinical, claims and social determinants of health (SDH) data. Addressing the challenge of predicting with only SDH we developed a novel framework termed Stratified Cascade Learning (SCL) and used it for predicting the risk of hospitalization (ROH).

Materials And Methods: The variable set includes 27 SDH and "age" and "sex" for a cohort of diabetic patients.

A Novel Anterior Bladder Tube for Traumatic Bladder Neck Contracture in Females: Initial Results.

Objective: To describe a novel tubularized bladder flap technique for repair of post-traumatic obliterate bladder neck and urethral stricture in women. Traumatic genitourinary injury in females is rare, and generally associated with pelvic fracture. Obliterate bladder neck is frequent in such cases.

Spermine-NBD as fluorescent probe for studies of the polyamine transport system in Leishmania donovani.

This study describes the synthesis of fluorescent probes as potential substrates for the polyamine transport system (PTS) of Leishmania donovani. A competitive radioassay was used to determine the most efficient probe. We observed that the conjugate spermine-nitrobenzofurazan (Spm-NBD) was able to compete with [H]-spermidine in L.

A case of febrile ulceronecrotic Mucha-Habermann disease with comorbidities.

Febrile ulceronecrotic Mucha-Habermann disease is a very rare and severe variant of pityriasis lichenoides et varioliformis acuta. Adult cases are difficult to diagnose as in the early course they can mimic erythema multiforme or lymphomatoid papulosis. We report a case of a 38-year-old woman who presented with 90% body surface area involvement, fever, diarrhea, malaise and associated comorbidities.

Comparison of Measured and Monte Carlo Calculated Dose Distributions from Indigenously Developed 6 MV Flattening Filter Free Medical Linear Accelerator.

Purpose: Monte Carlo simulation was carried out for a 6 MV flattening filter-free (FFF) indigenously developed linear accelerator (linac) using the BEAMnrc user-code of the EGSnrc code system. The model was benchmarked against the measurements. A Gaussian distributed electron beam of kinetic energy 6.

Synthesis and antikinetoplastid evaluation of bis(benzyl)spermidine derivatives.

This study describes the synthesis and the biological evaluation of twenty-four original bis(benzyl)spermidines. Structural modifications of the polyamine scaffold were performed in order to avoid easily metabolized bonds. Some bis(benzyl)polyamine derivatives have demonstrated promising activity in vitro against Trypanosoma brucei gambiense and Leishmania donovani.

Polyamine-based analogs and conjugates as antikinetoplastid agents.

Naturally occurring polyamines: putrescine, spermidine and spermine are crucial for Kinetoplastid growth and persistence. These aliphatic polycations are either biosynthesized or internalized into Kinetoplastid by active transport. Impairing the polyamine metabolism using polyamine derivatives is an interesting path in the search of new antikinetoplastid chemotherapy.

Synthesis and in vitro antikinetoplastid activity of polyamine-hydroxybenzotriazole conjugates.

Thirteen new polyamine derivatives coupled to hydroxybenzotriazole have been synthesized and evaluated for their in vitro antikinetoplastid activity. Trypanosoma Trypanothione reductase (TryR) was envisioned as a potential target. Among all tested molecules, only one compound, a N-spermidine-benzotriazole derivative, displayed relevant inhibitory activity on this enzyme but was not active on parasites.

Monte Carlo based investigations of electron contamination from telecobalt unit head in build up region and its impact on surface dose.

A Telecobalt unit has wide range of applications in cancer treatments and is used widely in many countries all around the world. Estimation of surface dose in Cobalt-60 teletherapy machine becomes important since clinically useful photon beam consist of contaminated electrons during the patient treatment. EGSnrc along with the BEAMnrc user code was used to model the Theratron 780E telecobalt unit.

Design, synthesis and in vitro antikinetoplastid evaluation of N-acylated putrescine, spermidine and spermine derivatives.

A structure-activity relationship study on polyamine derivatives led to the synthesis and the determination of antikinetoplastid activity of 17 compounds. Among them, a spermidine derivative (compound 13) was specifically active in vitro against Leishmania donovani axenic amastigotes (IC50 at 5.4μM; Selectivity Index >18.

Synthesis and biological evaluation of acridine derivatives as antimalarial agents.

New N-alkylaminoacridine derivatives attached to nitrogen heterocycles were synthesized, and their antimalarial potency was examined. They were tested in vitro against the growth of Plasmodium falciparum, including chloroquine (CQ)-susceptible and CQ-resistant strains. This biological evaluation has shown that the presence of a heterocyclic ring significantly increases the activity against P.

Design of 6Mev linear accelerator based pulsed thermal neutron source: FLUKA simulation and experiment.

The 6MeV LINAC based pulsed thermal neutron source has been designed for bulk materials analysis. The design was optimized by varying different parameters of the target and materials for each region using FLUKA code. The optimized design of thermal neutron source gives flux of 3×10(6)ncm(-2)s(-1) with more than 80% of thermal neutrons and neutron to gamma ratio was 1×10(4)ncm(-2)mR(-1).

Measurement of angular distribution of neutron flux for the 6MeV race-track microtron based pulsed neutron source.

The 6MeV race track microtron based pulsed neutron source has been designed specifically for the elemental analysis of short lived activation products, where the low neutron flux requirement is desirable. Electrons impinges on a e-gamma target to generate bremsstrahlung radiations, which further produces neutrons by photonuclear reaction in gamma-n target. The optimisation of these targets along with their spectra were estimated using FLUKA code.

Antimalarial acridines: synthesis, in vitro activity against P. falciparum and interaction with hematin.

A series of acridine derivatives were synthesised and their in vitro antimalarial activity was evaluated against one chloroquine-susceptible strain (3D7) and three chloroquine-resistant strains (W2, Bre1 and FCR3) of Plasmodium falciparum. Structure-activity relationship showed that two positives charges as well as 6-chloro and 2-methoxy substituents on the acridine ring were required to exert a good antimalarial activity. The best compounds possessing these features inhibited the growth of the chloroquine-susceptible strain with an IC(50)0.

Capns1, a new binding partner of RasGAP-SH3 domain in K-Ras(V12) oncogenic cells: modulation of cell survival and migration.

Ras GTPase-activating protein (RasGAP) is hypothesized to be an effector of oncogenic Ras stimulating numerous downstream cellular signaling cascades involved in survival, proliferation and motility. In this study, we identified calpain small subunit-1 (Capns1) as a new RasGAP-SH3 domain binding partner, using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation assay and was found specific to cells expressing oncogenic K-Ras.

Flavocytochrome b2: reactivity of its flavin with molecular oxygen.

Flavocytochrome b2, a flavohemoprotein, catalyzes the oxidation of lactate at the expense of the physiological acceptor cytochrome c in the yeast mitochondrial intermembrane space. The mechanism of electron transfer from the substrate to monoelectronic acceptors via FMN and heme b2 has been intensively studied over the years. Each prosthetic group is bound to a separate domain, N-terminal for the heme, C-terminal for the flavin.

Molecular tongs containing amino acid mimetic fragments: new inhibitors of wild-type and mutated HIV-1 protease dimerization.

We have designed, synthesized, and evaluated the inhibitory activity and metabolic stability of new peptidomimetic molecular tongs based on a naphthalene scaffold for inhibiting HIV-1 protease dimerization. Peptidomimetic motifs were inserted into one peptidic strand to make it resistant to proteolysis. The peptidic character of the molecular tongs can be decreased without changing the way they inhibit dimerization.