Deciphering the chemical constituents and antimicrobial activity of Prangos pabularia Lindl. using LC-MS/MS in combination with experimental evaluation and computational studies.

This study meticulously explores the antimicrobial potential of Prangos pabularia Lindl.'s aerial parts through a comprehensive blend of in vitro and in silico analysis. Extracts with varying polarities underwent LC-MS/MS identification of active components, followed by in vitro and in silico assessments of antimicrobial efficacy against Escherichia coli, Bacillus cereus, Candida albicans, Candida glabrata, and Candida paropsilosis. The methanolic extract exhibited significant antimicrobial activity with a MIC value of 48 µg/mL against all tested strains. Molecular docking revealed the compound 9-(3-methylbut-2-enoxy)-furo-(3,2-g)-chromen-7-one's highest binding affinity against the penicillin-binding protein (PBP) bacterial drug target molecule. Other compounds also displayed substantial interactions with key antimicrobial drug target proteins. Further, Molecular dynamics simulations affirmed the stability of protein and ligand conformations. Collectively, these results underscore Prangos pabularia Lindl.'s aerial parts as a promising botanical resource in combating diverse microbial infections. This comprehensive approach not only validates it's in vitro antimicrobial properties but also provides molecular insights into interaction mechanisms, advancing our comprehension of the plant's therapeutic potential.

Strategies Employed to Evade the Host Immune Response and the Mechanism of Drug Resistance in Mycobacterium tuberculosis: In Search of Finding New Targets.

The partial effectiveness of the host immune response to M. tuberculosis drives bacteria into a latent state, but it is difficult to eliminate the bacteria completely. Usually, this latent condition of M. tuberculosis is reversible, and reactivation of tuberculosis is the leading cause of the majority of transmission. A number of studies performed on animal models and humans have not yet provided a detailed understanding of the mechanisms or correlates of immunity of M. tuberculosis infection or why there is a significant immunity failure to remove the pathogen. Moreover, the mechanism of resistance involved in drug-resistant M. tuberculosis leads to the emergence of strains of bacteria that show significant resistance to the majority of anti-tuberculosis drugs. We have also provided the recent findings and trends regarding the development of new drug molecules to treat drug and multidrug-resistant tuberculosis and the advancements in immunotherapy in the treatment of drug-resistant tuberculosis. This article provides an in-depth and critical analysis of various strategies employed by the drug-resistant M. tuberculosis to escape the host immune response. This bacterium persists in the host for a longer period of time and leads to the development of tuberculosis infection. Furthermore, we also discussed the new targets for the effective treatment of drug-resistant tuberculosis.

Development of New Therapeutics to Meet the Current Challenge of Drug Resistant Tuberculosis.

Tuberculosis (TB) is a prominent infective disease and a major reason of mortality/ morbidity globally. Mycobacterium tuberculosis causes a long-lasting latent infection in a significant proportion of human population. The increasing burden of tuberculosis is mainly caused due to multi drug-resistance. The failure of conventional treatment has been observed in large number of cases. Drugs that are used to treat extensively drug-resistant tuberculosis are expensive, have limited efficacy, and have more side effects for a longer duration of time and are often associated with poor prognosis. To regulate the emergence of multidrug resistant tuberculosis, extensively drug-resistant tuberculosis and totally drug resistant tuberculosis, efforts are being made to understand the genetic/molecular basis of target drug delivery and mechanisms of drug resistance. Understanding the molecular approaches and pathology of Mycobacterium tuberculosis through whole genome sequencing may further help in the improvement of new therapeutics to meet the current challenge of global health. Understanding cellular mechanisms that trigger resistance to Mycobacterium tuberculosis infection may expose immune associates of protection, which could be an important way for vaccine development, diagnostics, and novel host-directed therapeutic strategies. The recent development of new drugs and combinational therapies for drug-resistant tuberculosis through major collaboration between industry, donors, and academia gives an improved hope to overcome the challenges in tuberculosis treatment. In this review article, an attempt was made to highlight the new developments of drug resistance to the conventional drugs and the recent progress in the development of new therapeutics for the treatment of drugresistant and non-resistant cases.

Nano-Drug Delivery Systems: Possible End to the Rising Threats of Tuberculosis.

Tuberculosis (TB) is still one of the deadliest disease across the globe caused by Mycobacterium tuberculosis (Mtb). Mtb invades host macrophages and other immune cells, modifies their lysosome trafficking proteins, prevents phagolysosomes formation, and inhibits the TNF receptor-dependent apoptosis in macrophages and monocytes. Tuberculosis (TB) killed 1.4 million people worldwide in the year 2019. Despite the advancements in tuberculosis (TB) treatments, multidrugresistant tuberculosis (MDR-TB) remains a severe threat to human health. The complications are further compounded by the emergence of MDR/XDR strains and the failure of conventional drug regimens to eradicate the resistant bacterial strains. Thus, new therapeutic approaches aim to ensure cure without relapse, to prevent the occurrence of deaths and emergence of drug-resistant strains. In this context, this review article summarises the essential nanotechnology-related research outcomes in the treatment of tuberculosis (TB), including drug-susceptible and drug-resistant strains of Mtb. The novel anti-tuberculosis drug delivery systems are also being detailed. This article highlights recent advances in tuberculosis (TB) treatments, including the use of novel drug delivery technologies such as solid lipid nanoparticles, liposomes, polymeric micelles, nano-suspensions, nano-emulsion, niosomes, liposomes, polymeric nanoparticles and microparticles for the delivery of anti-TB drugs and hence eradication and control of both drug-susceptible as well as drug-resistant strains of Mtb.

Impact of COVID-19 on surgical residency programs in Pakistan; A residents' perspective. Do programs need formal restructuring to adjust with the "new normal"? A cross-sectional survey study.

BACKGROUND: Due to high-risk exposure of surgical residents to coronavirus, surgical residency programs have changed their training methods and working hours drastically. The purpose of this study is to find out the positive and negative impacts of the pandemic on surgical residency programs and on the lives of surgical residents. MATERIALS AND METHODS: A cross-sectional study was conducted on 112 surgical residents of a tertiary care hospital in Pakistan, with a mean age of 30.5 years from all the departments of surgery using a self-made, validated 40-point questionnaire comprising three sections. The last section also included modified Maslach Burnout inventory. RESULTS: Of all the residents, 97 (86.6%) stated that their surgical hands-on duration is adversely affected by the pandemic. As for clinical exposure, 92 (82.1%) trainees responded that their clinical exposure is affected too. Among all the subjects, 69 (61%) were concerned about transmitting it to their family members and 43 (38.4%) affirmed on being afraid of dying because of their direct exposure. On the brighter side, the average number of working hours per week for surgical residents were reduced from 81.10 ± 6.21 to 49.16 ± 6.25 (p < 0.001) due to the outbreak. Modified Maslach Burnout inventory score was 8.33 ± 2.34 after the outbreak, showing statistically significant reduction in burnout among the surgical residents (p < 0.001). CONCLUSION: The changes in the surgical residency programs amidst the pandemic has reduced the working hours, hands-on and clinical exposure of the surgical residents. Moreover, the situation has provided an opportunity to explore efficient methods of learning that can lead to lesser burnout. However, psychological burdens of surgical residents like fear of acquiring the infection should be appropriately addressed.

Retraction Note to: Occurrence, spread and control measures of Bothriocephalus acheilognathi (Bothriocephalidae: Cestoda).

[This retracts the article DOI: 10.1007/s12639-014-0568-6.].

Use of preputial skin for coverage of post-burn contractures of fingers in children.

OBJECTIVE: Hand burns are common injuries. Children frequently sustain burn injuries, especially to their hands. Contractures are a common sequel of severe burns around joints. The prepuce, or foreskin, has been used as a skin graft for a number of indications. We conducted this study to evaluate the feasibility of utilising the preputial skin for the management of post-burn contractures of fingers in uncircumcised male children. MATERIALS AND METHODS: Preputial skin was used for the coverage of released contractures of fingers in 12 patients aged 2-6 years. The aetiology of burns was "Kangri" burn in eight patients and scalding in four patients. Six patients had contracture in two fingers, four patients in one finger, and two patients had contractures in three fingers. RESULTS: None of the patients had graft loss, and all the wounds healed within 2 weeks. All patients had complete release of contractures without any recurrence. Hyperpigmentation of the grafts was observed over a period of time, which was well accepted by the parents. CONCLUSIONS: Preputial skin can be used successfully for male children with mild-to-moderate contractures of 2-3 fingers for restoration of the hand function, minimal donor site morbidity.