Impact of Biological Sex on Radar-Measured Heart Sound Quality.

Radar based contact-free technology has number of potential applications for monitoring the cardiopulmonary functions of patients. However, no study has evaluated the effect of gender on the quality of the recordings. This study makes an attempt to distinguish radar based recording of male and female subjects. The study analysed a publicly available dataset of radar-recorded heart sound signals from both male and female subjects. Here, we exploit the reference signal-to-noise ratio (RSNR) to quantify the signal's quality. The results indicate that there is a significant difference in the signal quality between males and females, with males having a higher RSNR value compared to females. This could be a limitation in the widespread use of the current radar based cardiopulmonary recording techniques and overcoming this should be considered for future research.Clinical relevance- This work has highlighted the gender based difference. By considering this, the radar based cardiopulmonary device has the potential for being used for patients requiring long-term monitoring.

Direct evidence of terahertz emission arising from anomalous Hall effect.

A detailed understanding of the different mechanisms being responsible for terahertz (THz) emission in ferromagnetic (FM) materials will aid in designing efficient THz emitters. In this report, we present direct evidence of THz emission from single layer Co[Formula: see text]Fe[Formula: see text]B[Formula: see text] (CoFeB) FM thin films. The dominant mechanism being responsible for the THz emission is the anomalous Hall effect (AHE), which is an effect of a net backflow current in the FM layer created by the spin polarized current reflected at the interfaces of the FM layer. The THz emission from the AHE-based CoFeB emitter is optimized by varying its thickness, orientation, and pump fluence of the laser beam. Results from electrical transport measurements show that skew scattering of charge carriers is responsible for the THz emission in the CoFeB AHE-based THz emitter.

Targeting Vancomycin-Resistant Enterococci (VRE) Infections and Van Operon-Mediated Drug Resistance Using Dimeric Cholic Acid-Peptide Conjugates.

Emergence of vancomycin resistance in Gram-positive bacteria and the prevalence of vancomycin-resistant Enterococci (VRE) infections are highly alarming as very limited antibiotic options are available against VRE infections. Here, we present the synthesis of cholic acid-derived dimeric amphiphiles where two cholic acid moieties are tethered through carboxyl terminals using different alkylene spacers. Our investigations revealed that dimer 5 possessing a propylene spacer and glycine-valine peptides tethered on hydroxyl groups is the most effective antimicrobial against VRE. Dimer 5 can permeabilize bacterial membranes, generate reactive oxygen species, and clear preformed biofilms. We further demonstrate that dimer 5 downregulates vancomycin-mediated transcriptional activation of the vanHAX gene cluster and does not allow VSE to develop vancomycin resistance until 100 generations. Therefore, this study, for the first time, presents a bacterial membrane-targeting amphiphile that can mitigate VRE infections and inhibit the emergence of vancomycin resistance.

Development of a Highly Specific, Selective, and Sensitive Fluorescent Probe for Detection of Mycobacteria in Human Tissues.

Tuberculosis (TB), including extrapulmonary TB, is responsible for more than one million deaths in a year worldwide. Existing methods of mycobacteria detection have poor sensitivity, selectivity, and specificity, especially in human tissues. Herein, the synthesis of a cholic acid-derived fluorescent probe (P4) that can specifically stain the mycobacterium species is presented. It is shown that P4 probe specifically binds with mycobacterial lipids, trehalose monomycolate, and phosphatidylinositol mannoside 6. P4 probe can detect mycobacteria in polymicrobial planktonic cultures and biofilms with high specificity, selectivity, and sensitivity. Moreover, it can detect a single mycobacterium in the presence of 10 000 other bacilli. Unlike the probes that depend on active mycobacterial enzymes, the membrane-specific P4 probe can detect mycobacteria even in formalin-fixed paraffin-embedded mice and human tissue sections. Therefore, the ability of the P4 probe to detect mycobacteria in different biological milieu makes it a potential candidate for diagnostic and prognostic applications in clinical settings.

Nonimmunogenic Hydrogel-Mediated Delivery of Antibiotics Outperforms Clinically Used Formulations in Mitigating Wound Infections.

Treatment of chronic wound infections caused by Gram-positive bacteria such as Staphylococcus aureus is highly challenging due to the low efficacy of existing formulations, thereby leading to drug resistance. Herein, we present the synthesis of a nonimmunogenic cholic acid-glycine-glycine conjugate (A6) that self-assembles into a supramolecular viscoelastic hydrogel (A6 gel) suitable for topical applications. The A6 hydrogel can entrap different antibiotics with high efficacy without compromising its viscoelastic behavior. Activities against different bacterial species using a disc diffusion assay demonstrated the antimicrobial effect of the ciprofloxacin-loaded A6 hydrogel (CPF-Gel). Immune profiling and gene expression studies after the application of the A6 gel to mice confirmed its nonimmunogenic nature to host tissues. We further demonstrated that topical application of CPF-Gel clears S. aureus-mediated wound infections more effectively than clinically used formulations. Therefore, cholic acid-derived hydrogels are an efficacious matrix for topical delivery of antibiotics and should be explored further.

Cholic-Acid-Derived Amphiphiles Can Prevent and Degrade Fungal Biofilms.

Infections caused by fungal species via their existence as biofilms on medical devices can cause organ damage via candidiasis and candidemia. Different Candida species like Candida albicans can pose a serious threat by resisting host's immune system and by developing drug resistance against existing antimycotic agents. Therefore, targeting of fungal membranes can be used as an alternative strategy to combat the fungal infections. Here, we present screening of different amphiphiles based on cholic acid against different Candida strains as these amphiphiles can act as potent membrane-targeting antimycotic agents. Structure-activity correlations, biochemical assays and electron microscopy studies showed that amphiphiles having 4 and 6 carbon chains are most potent, safe and can act on the fungal membranes. Candida albicans did not show emergence of drug resistance on repeated usage of these amphiphiles unlike fluconazole. We show that these amphiphiles can prevent the formation of biofilms and also have the ability to degrade preformed biofilms on different substrates including acrylic teeth. We further demonstrate that amphiphiles 4 and 6 can clear the Candida albicans wound infections and prevent the biofilm formation on indwelling devices in murine models. Therefore, amphiphiles derived from cholic acid and their coatings provide suitable alternatives for inhibiting the fungal infections.

Cholic Acid-Derived Amphiphile which Combats Gram-Positive Bacteria-Mediated Infections via Disintegration of Lipid Clusters.

Inappropriate and uncontrolled use of antibiotics results in the emergence of antibiotic resistance, thereby threatening the present clinical regimens to treat infectious diseases. Therefore, new antimicrobial agents that can prevent bacteria from developing drug resistance are urgently needed. Selective disruption of bacterial membranes is the most effective strategy for combating microbial infections as accumulation of genetic mutations will not allow for the emergence of drug resistance against these antimicrobials. In this work, we tested cholic acid (CA) derived amphiphiles tethered with different alkyl chains for their ability to combat Gram-positive bacterial infections. In-depth biophysical and biomolecular simulation studies suggested that the amphiphile with a hexyl chain (6) executes more effective interactions with Gram-positive bacterial membranes as compared to other hydrophobic counterparts. Amphiphile 6 is effective against multidrug resistant Gram-positive bacterial strains as well and does not allow the adherence of S. aureus on amphiphile 6 coated catheters implanted in mice. Further, treatment of wound infections with amphiphile 6 clears the bacterial infections. Therefore, the current study presents strategic guidelines in design and development of CA-derived membrane-targeting antimicrobials for Gram-positive bacterial infections.

Preemptive Analgesia by Intraperitoneal Instillation of Ropivacaine in Laparoscopic Cholecystectomy.

BACKGROUND: Preemptive analgesia has the potential to be more effective than a similar analgesic treatment initiated after surgery as it reduces immediate postoperative pain as well as chronic pain. AIM: To study the efficacy of preemptive analgesia with intraperitoneal instillation of ropivacaine in laparoscopic cholecystectomy (LC). MATERIALS AND METHODS: This prospective randomized double-blind study was conducted on patients undergoing LC. Hundred patients were randomly divided into two groups of fifty each. In Group A, patients received 3 mg/kg of ropivacaine intraperitoneal instillation in 100 ml normal saline (NS) before creation of pneumoperitoneum and in Group B patients received 3 mg/kg of ropivacaine intraperitoneal instillation in 100 ml NS after completion of surgery. Postoperative visual analog scale score for abdominal and shoulder tip pain alongwith requirement of rescue analgesic were recorded for 24 h. RESULTS: Significantly lower visual analog scores for pain were observed in Group A versus Group B. Group A reported significantly lower pain at 0 h (P < 0.001), 1 h (P = 0.003), 3 h (P = 0.006), 6 h (P = 0.003), and 12 h (P = 0.001) postoperatively, but the difference was not statistically significant after 12 h. The mean time of first rescue analgesic was 472.8 ± 26.32 min in Group A, as compared with 189 ± 11.87 min in Group B. A significantly lower analgesic requirement was observed in Group A versus Group B throughout the entire study period (P < 0.05). CONCLUSION: The preemptive analgesia with intraperitoneal instillation of ropivacaine before creation of pneumoperitoneum is much more effective for postoperative pain relief in comparison to intraperitoneal instillation of ropivacaine after completion of surgery.