Exploring α, ß-unsaturated carbonyl compounds against bacterial efflux pumps via computational approach.

Antibiotic resistance has become a pressing global health crisis, with bacterial infections increasingly difficult to treat due to the emergence of multidrug resistance. This study aims to identify potential chalcone molecules that interact with two key multidrug efflux pumps, AcrB and EmrD, of Escherichia coli, using advanced computational tools. In silico ADMET (absorption, distribution, metabolism, excretion, and toxicity), drug-likeness prediction, molecular docking, and molecular dynamics simulation analyses were conducted on a ligand library comprising 100 chalcone compounds against AcrB (PDB: 4DX5) and EmrD (PDB: 2GFP). The results demonstrated that Elastichalcone A (PubChem CID 102103730) exhibited a remarkable binding affinity of -9.9 kcal/mol against AcrB, while 4'-methoxy-4-hydroxychalcone (PubChem CID 5927890) displayed a binding affinity of -9.8 kcal/mol against EmrD. Both ligands satisfied drug-likeness rules and possessed favorable pharmacokinetic profiles. Molecular dynamics simulation of the AcrB-Elastichalcone A complex remained stable over 100 ns, with minimal fluctuations in root-mean-square deviation and root-mean-square fluctuation. The screened ligand library demonstrated good drug-likeness and pharmacokinetic properties. Moreover, the MM/PB(GB)SA calculation indicated the tight binding and thermodynamic stability of the simulated protein-ligand complexes. Overall, this study highlights the potential of chalcones as promising candidates for targeting multidrug efflux pumps, offering a potential strategy to overcome antibiotic resistance. Further exploration and optimization of these compounds may lead to the development of effective therapeutics against multidrug-resistant bacterial infections.Communicated by Ramaswamy H. Sarma.

Plethora of adverse drug reactions in geriatric population receiving statin therapy for dyslipidaemia.

Background: Hyperlipidemia plays a major role in the pathogenesis of cardiovascular diseases (CVD). Statins are considered to be the most efficacious drugs in the management of hyperlipidemia and this class of drugs is most commonly prescribed for the treatment of hyperlipidemias. Although statin therapy has transformed the management of hyperlipidemia, it is associated with the skeletal muscle, neurological, and metabolic adverse effects. This study was conducted to evaluate the adverse effects of statin therapy in a geriatric population which may help in understanding whether these effects are dose-dependent. Methods: The study was conducted on 200 patients receiving statin therapy (atorvastatin and rosuvastatin) for hyperlipidemias. They were divided into four groups depending on the prescribed dose of atorvastatin and rosuvastatin. All study subjects were followed up for 6 months. The adverse effects reported by them during the statin therapy were documented and analyzed. Results: All patients reported adverse effects after the initiation of statin therapy. Headache and muscle symptoms were among the most commonly reported adverse effects. There was no serious adverse effect (SAE). None of the adverse effects led to the discontinuation of the statin therapy. Conclusion: The results of this study suggest that all patients receiving statin therapy experience one or more adverse effects during the therapy. The adverse effects were not found to be severe in the geriatric age group.

Hydrocortisone, Vitamin C and thiamine for the treatment of sepsis and septic shock following cardiac surgery.

BACKGROUND AND AIMS: The effect of vitamin C on vasopressor requirement in critically ill patients have been evaluated previously. We aimed to evaluate the effect of vitamin C, hydrocortisone and thiamine on vasopressor requirement and mortality in post-operative adult cardiac surgical patients with septic shock. METHODS: About 24 patients with septic shock were randomised into Group 1 (receiving matching placebo per day for 4 days) and Group 2 (receiving 6 g vitamin C, 400 mg thiamine and 200 mg hydrocortisone per day for 4 days). Vasopressor dose over 4 days of therapy was the primary endpoint, whereas in-hospital mortality was the secondary endpoint. RESULTS: APACHE IV and EUROSCORE II scores were similar between both the groups. Significant reductions in the requirement of vasopressin (difference from day 1 - 0.0008 ± 0.00289 vs 0.0033 ± 0.00492 units/kg/min; P = 0.019) and noradrenaline (difference from day 1 - 0.0283 ± 0.040 vs 0.023 ± 0.035 µg/kg/min; P = 0.006) were observed with vitamin C treatment as compared to control group. PCT levels on Day 3 (68.11 ± 33.64 vs 33.2 ± 27.55 ng/mL; P = 0.0161) and Day 4 (70.03 ± 29.74 vs 26.3 ± 23.08 ng/mL; P = 0.0009) were significantly lower in treatment group as compared to control. However, there was no difference in the Sepsis-Related Organ Failure Assessment (SOFA) score and mortality between the studied groups. CONCLUSION: Combination of vitamin C, thiamine and hydrocortisone reduces vasopressor requirement in adult cardiac surgical patients with septic shock.

Efficacy of centrifuged liquid-based cytology over conventional cytology: A comparative study.

BACKGROUND: Exfoliative cytology is the microscopic examination of a shed or desquamated cells from the epithelial surface. Centrifuged liquid-based cytology (CLBC) is a modified technique that is used in the current study. AIMS: To compare the efficacy of CLBC with conventional cytology in apparently normal mucosa and histologically proven cases of oral squamous cell carcinoma after staining with Papanicolaou stain. MATERIALS AND METHODS: The study sample was collected from fifty individuals with no habits and apparently normal oral mucosa (Group 1) and forty cases of histologically proven cases of oral squamous cell carcinoma (Group 2). One smear was taken and spread on the slide by a conventional technique. The second sample was flushed out in a suspending solution, centrifuged, and the cell pellet obtained was used to make the smear. The stained smears were compared for nine parameters such as adequate cellularity, clear background, uniform distribution, cellular overlapping, cellular elongation, mucus, inflammatory blood, and microbial colonies. Chi-square test was used for statistical analysis and P ≤ 0.05 was considered statistically significant. RESULTS: There was a statistically significant result with parameters such as adequate cellularity, clear background, uniform distribution, cellular overlapping, and cellular elongation in CLBC technique, in comparison with the conventional technique. The presence of mucus, microbial colonies, and inflammatory cells were also less in CLBC technique in comparison with the conventional technique. CONCLUSION: CLBC has better efficacy over conventional method in all the parameters analyzed.

Portable mTBI Assessment Using Temporal and Frequency Analysis of Speech.

This paper shows that extraction and analysis of various acoustic features from speech using mobile devices can allow the detection of patterns that could be indicative of neurological trauma. This may pave the way for new types of biomarkers and diagnostic tools. Toward this end, we created a mobile application designed to diagnose mild traumatic brain injuries (mTBI) such as concussions. Using this application, data were collected from youth athletes from 47 high schools and colleges in the Midwestern United States. In this paper, we focus on the design of a methodology to collect speech data, the extraction of various temporal and frequency metrics from that data, and the statistical analysis of these metrics to find patterns that are indicative of a concussion. Our results suggest a strong correlation between certain temporal and frequency features and the likelihood of a concussion.

Improvization of conventional cytology by centrifuged liquid-based cytology in oral exfoliative cytology specimen.

BACKGROUND: Exfoliative cytology is the microscopic examination of shed or desquamated cells from the epithelial surface. Centrifuged liquid-based cytology (CLBC) is a modified technique that was used in the current study. AIMS: To compare the efficacy of CLBC with conventional cytology in apparently normal mucosa after staining with Papanicolaou (PAP) stain. MATERIALS AND METHODS: Fifty cases of apparently normal mucosa from healthy subjects were selected for the study. The first sample was taken and spread on the slide by the conventional technique. The second sample was flushed out in a suspending solution, centrifuged, and the cell pellet obtained was used to make the smear. The stained smears were compared for seven parameters such as adequate cellularity, clear background, uniform distribution, cellular overlapping, cellular elongation, mucus, and inflammatory cells. Chi-square test was used for statistical analysis and P ≤ 0.05 was considered to be statistically significant. RESULTS: There was a statistically significant difference between CLBC and conventional cytology with parameters such as adequate cellularity (P = 0.001), clear background (P = 0.001), uniform distribution (0.005), cellular overlapping, and cellular elongation (P = 0). The presence of mucus and inflammatory cells was minimal as the samples were collected from healthy subjects. CONCLUSION: CLBC has better efficacy over the conventional method in all the parameters analyzed.

Micrometastasis Detection using Special Stains in Nodal Tissues of Oral Squamous Cell Carcinoma - A Histochemical Study.

INTRODUCTION: Micrometastasis to the lymph node is an important prognostic factor in survival and recurrence and even in making critical decisions regarding postoperative radiation treatment. Methods like Immunohistochemistry (IHC), serial sectioning and Polymerase Chain Reaction (PCR) are very sensitive; however, they are expensive and time consuming. Hence, there is a need for the detection of micrometastasis by method which is easily feasible and inexpensive. AIM: This study was undertaken to identify if special stains (Modified Papanicolaou stain and Ayoub Shklar stain) are valuable in detecting micrometastasis which are routinely missed in Haematoxylin and Eosin stain and also to compare their efficacy over Haematoxylin and Eosin stain in detection of metastatic tumour cells in non-metastatic lymph nodes. MATERIALS AND METHODS: This study constituted a total of 300 histopathologically proven non metastatic lymph node sections. Other than Haematoxylin and Eosin stain, Modified Papanicalaou and Ayoub Shklar stain were used for identification of micrometastatic deposit. RESULTS: Papanicolaou stain was the only stain useful in detecting micrometastasis which accounted to 7% of non metastatic lymph node sections used in our study. CONCLUSION: Papanicolaou stain has definitely proved valuable in detecting micrometastasis over routine Haematoxylin and Eosin and Ayoub Shklar stain with an added advantage of being economical, easily available and technique insensitive.

Does scorpion bite lead to development of resistance to the effect of local anaesthetics?

A patient posted for vaginal hysterectomy was administered subarachnoid block, which failed, so was repeated in one space above. The block failed again, after waiting for 30 min. Patient gave a history of scorpion bite twice, once at the age of 17 years on her right foot and again about 8 months back. Thereafter, balanced general anaesthesia was given. On eighth post-operative day, after explaining about her possible special condition (?Resistance to local anaesthetic agents), the patient was given left median, ulnar and radial nerve blocks at the wrist and local infiltration near the anatomical snuff box. There was neither sensory nor motor block. The scorpion venom is known to affect the pumping mechanism of sodium channels in the nerve fibres, which are involved in the mechanism of action of local anaesthetic drugs, it may be responsible for the development of 'resistance' to the action of local anaesthetic agents.