Synthesis of 1,2,3-triazole tethered bifunctional hybrids by click chemistry and their cytotoxic studies

In view of the drug resistance with most of the currently used anticancer drugs, molecular hybrids of pyrazolyl chalcones and p-nitro benzyl functionalities tethered by triazole ring have been synthesised and evaluated for cytotoxic studies against three human cancer cell lines (THP, COLO-205, A-549). The results of the preliminary investigation exhibited marked dependence of the cytotoxic activity on the electronic factors. Placement of naphthyl (JGPT-11) and trimethoxy phenyl ring (JGPT-6) as ring A proved to be extremely beneficial in enhancing the cytotoxic potential. Thus we herein report the synthesis and cytotoxic studies of a new class of molecular hybrids. Detailed investigation on the biological mechanistic insights of JGPT-11 and 6 is under progress.     

Role of polymer–drug conjugates in organ-specific delivery systems

Polymers have been utilized to deliver the drug to targeted site in controlled manner, achieving the high-therapeutic efficacy. Polymeric drug conjugates having variable ligands as attachments have been proved to be biodegradable, stimuli sensitive and targeted systems. Numerous polymeric drug conjugates having linkers degraded by acidity or intracellular enzymes or sensitive to over expressed groups of diseased organ/tissue have been synthesized during last decade to develop targeted delivery systems. Most of these organs have number of receptors attached with different cells such as Kupffer cells of liver have mannose-binding receptors while hepatocytes have asialoglycoprotein receptors on their surface which mainly bind with the galactose derivatives. Such ligands can be used for achieving high targeting and intracellular delivery of the drug. This review presents detailed aspects of receptors found in different cells of specific organ and ligands with binding efficiency to these specific receptors. This review highlights the need of further studies on organ-specific polymer–drug conjugates by providing detailed account of polymeric conjugates synthesized till date having organ-specific targeting.     

Heterogeneity of Randomized Controlled Trials of Fecal Microbiota Transplantation in Recurrent Clostridioides difficile Infection

Digestive Diseases and Sciences - Clinical trials have demonstrated the efficacy of FMT for reduction in CDI recurrences (rCDI), but this treatment and its reporting in the literature has...     

Flexible Thin-Film PVDF-TrFE Based Pressure Sensor for Smart Catheter Applications

We demonstrate the design of thin flexible pressure sensors based on piezoelectric PVDF-TrFE (polyvinyledenedifluoride-tetrafluoroethylene) co-polymer film, which can be integrated onto a catheter, where the compact inner lumen space limit the dimensions of the pressure sensors. Previously, we demonstrated that the thin-film sensors of one micrometer thickness were shown to have better performance compared to the thicker film with no additional electrical poling or mechanical stretching due to higher crystallinity. The pressure sensors can be mass producible using standard lithography process, with excellent control of film uniformity and thickness down to one micrometer. The fabricated pressure sensors were easily mountable on external surface of commercial catheters. Elaborate experiments were performed to demonstrate the applicability of PVDF sensors towards catheter based biomedical application. The resonant frequency of the PVDF sensor was found to be 6.34 MHz. The PVDF sensors can operate over a broad pressure range of 0–300 mmHg. The average sensitivity of the PVDF sensor was found to be four times higher (99 μV/mmHg) than commercial pressure sensor while the PVDF sensor (0.26 s) had fivefold shorter response time than commercial pressure sensor (1.30 s), making the PVDF sensors highly suitable for real-time pressure measurements using catheters.     

Reporting of dose–volume specifications for “Martinez Universal Perineal Interstitial Template–based interstitial high-dose-rate brachytherapy for gynecological cancers” according to International Commission on Radiation Units and Measurements 58 with early clinical outcomes

PurposeThe study is an audit of reporting dose and volume specifications as per the ICRU 58 for MUPIT-based interstitial brachytherapy in gynecological cancers. Correlation between total reference air kerma (TRAK) and isodose surface was also evaluated to understand the intensity of treatment in interstitial brachytherapy.Methods and MaterialsForty-two patients underwent HDR MUPIT-based interstitial brachytherapy 20 Gy in five fractions after EBRT during 2017–2019. Treated volume, high and low-dose regions, mean central dose, Dose Homogeneity Index (DHI), organ at risk doses, and TRAK values were computed.ResultsHigh-dose regions V150 mean was 12.4 cc and V200 was 4.58 cc; and low-dose region was 75.92 cc. The mean treated volume was 59.8 cc. The mean central dose was 3.7 Gy. DHI was 79%. The mean D2cm³ bladder and rectum were 2.9 Gy and 2.8 Gy. The mean TRAK was 0.16 cGy per fraction per hour at 1 m. TRAK values showed significant correlation with various isodose volumes (TRAK and V100: r = 0.943 p < 0.0005; and TRAK and V50: r = 0.953; p < 0.0005). A positive correlation was observed between TRAK and the number of needles (r = 0.746; p < 0.0005). At a median followup of 16 months, 4 of 42 patients (9.5%) had local recurrences.ConclusionsOur study shows compliance with ICRU 58 recommendations along with certain deviations. Local recurrence rate is acceptable. TRAK shows correlation with surface isodose in MUPIT-based brachytherapy and should to be evaluated in future studies.     

Predictors of failure after fecal microbiota transplantation for recurrent Clostridioides difficile infection: a systematic review and meta-analysis

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI), with ~15% 1-year recurrence rate. Small studies have identified variable risk factors associated with FMT failure. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of FMT failure. A systematic search of Medline, Embase, and Web of Science was performed from January 2013 up to June 2020. Meta-analyses were performed using random-effects models and pooled adjusted odds ratios for risk factors reported in ≥2 studies were calculated. Overall, 2671 patients with recurrent CDI who underwent FMT in 12 studies were included. FMT failure occurred in 454 patients (16.9%) with median follow-up of 3 months (range 2–7.7 months). A total of 9 risk factors were identified in ≥2 studies. Meta-analysis showed that use of non- CDI antibiotics, presence of inflammatory bowel disease, poor quality of bowel preparation, CDI-related hospitalization before FMT, inpatient FMT, and severe CDI were associated with statistically significant increased risk of failure after FMT. Increasing age, female gender, and immunocompromised status were not associated with increased risk for FMT failure. Several risk factors (both modifiable and non-modifiable) are associated with FMT failure. Lower use of antibiotics in the post-FMT period and good bowel preparation at the time of FMT are associated with lower risk of failure after FMT. Additionally, patients with non-modifiable risk factors should be counseled to be particularly alert about recurrent symptoms after FMT.