Antifungal activity of novel azetidine tethered chitosan synthesized via multicomponent reaction approach.

The increasing incidences of fungal infections among Covid-19 infected patients is a global public concern and urgently demands novel antifungals. Biopolymers like chitosan hold unique structural properties and thus can be utilized in the synthesis of biologically important scaffolds. To address the current scenario, the author's synthesized novel chitosan-azetidine derivative by adopting one-pot multicomponent reaction approach. The influence of chemical modification on the structural characteristics was investigated by means of spectroscopic techniques viz. FT-IR and 1HNMR and elemental analysis. Additionally, the authors investigated the antifungal potential of chitosan-azetidine derivative against Aspergillus fumigatus 3007 and the results indicated higher antifungal effect with an antifungal inhibitory index of 26.19%. The SEM and confocal microscopy images also reflected a significant inhibitory effect on the morphology of fungal mycelia, thus reflecting the potential of synthesized chitosan-azetidine derivativeas a potential antifungal agent.

Polysaccharides and lipoproteins as reactants for the synthesis of pharmaceutically important scaffolds: A review.

The growing number of diseases in the past decade has once again highlighted the need for extensive research on the development of novel drugs. There has been a major expansion in the number of people suffering from malignant diseases and types of life-threatening microbial infections. The high mortality rates caused by such infections, their associated toxicity, and a growing number of microbes with acquired resistance necessitate the need to further explore and develop the synthesis of pharmaceutically important scaffolds. Chemical entities derived from biological macromolecules like carbohydrates and lipids have been explored and observed to be effective agents in the treatment of microbial infections and diseases. These biological macromolecules offer a variety of chemical properties that have been exploited for the synthesis of pharmaceutically relevant scaffolds. All biological macromolecules are long chains of similar atomic groups which are connected by covalent bonds. By altering the attached groups, the physical and chemical properties can be altered and molded as per the clinical applications and needs, this ring them potential candidates for drug synthesis. The present review establishes the role and significance of biological macromolecules by articulating various reactions and pathways reported in the literature.

Carbohydrate hitched imidazoles as agents for the disruption of fungal cell membrane.

The fungal diseases represent an increasing global health burden and have transformed from a rare curiosity to the leading cause of human mortality. The present manuscript reports the antifungal potential of two novel compounds possessing a carbohydrate and an imidazole moiety. Antifungal susceptibility test determined the growth inhibition potential of the synthesized compounds against Aspergillus niger 9689 and it was observed that compounds D and E gave an antifungal inhibitory index of 66.66 and 56.67% respectively. Further, ultra-structure analysis of the treated fungal mycelia through scanning electron microscope (SEM) and confocal microscopy indicated significant membrane permeability and disintegration of fungal cell membrane, thus highlighting the probable role of the synthesized compounds as inhibitors of fungal lanosterol 14α-demethylase. In silico studies corroborated with the in-vitro results, as the synthesized compounds interacted with the critical amino acids present at the active site of the fungal enzyme (lanosterol 14α-demethylase).

Effect of intratympanic steroid administration on sensorineural hearing loss associated with acute otitis media.

OBJECTIVE: To evaluate a small cohort of patients who presented with symptoms and signs consistent with acute infective sensorineural hearing loss who were treated with intratympanic steroids. METHOD: Seven patients received a 7-day course of oral antibiotics and oral prednisolone followed by 3 intratympanic injections of methylprednisolone and 1 week of topical dexamethasone drops. RESULTS: Hearing improved in 57 per cent of patients (four out of seven). The mean improvement in this group was 24 dB (range, 10-52 dB). The magnitude of the sensorineural hearing loss at presentation was less in those who responded to intratympanic steroid therapy than in non-responders (mean pure tone average of 30 dB versus 65 dB pre-intratympanic steroids, and 14 dB versus 83 dB post-intratympanic steroids, respectively). CONCLUSION: The results of our study suggest that intratympanic steroids provide a valuable contribution to the treatment of acute infective sensorineural hearing loss and may provide additional benefit by virtue of a concentrated local steroid effect in patients who do not respond to antibiotics.

Phenotypic expression of blast resistance gene Pi54 is not affected by its chromosomal position.

KEY MESSAGE: This is a novel report in which chromosomal position of the rice blast resistance gene Pi54 was not found to affect significantly the resistance phenotype or morphological traits. Blast disease caused by Magnaporthe oryzae is a serious constraint in rice production at global level. Pi54 gene imparts resistance against M. oryzae. Three different transgenic lines containing Pi54 and its orthologue Pi54rh were shown to be resistant to different races of M. oryzae. To determine the chromosomal location of Pi54 gene in transgenic lines, inverse PCR was performed. Our analysis showed that in two transgenic lines, Pi54 gene was integrated on chromosomes 6 and 10 at 12.94 and 22.30 Mb, respectively. Similarly, Pi54rh allele was integrated on chromosome 1 at 16.25 Mb. The Pi54 gene present on chromosome 6 was located in a non-coding region whereas in the other TP-Pi54 line, the gene was introgressed on chromosome 10 in between the coding region of SAP domain gene. The Pi54rh was also located in the non coding region flanked by the retrotransposon genes. These rice lines were evaluated for eight different traits related to seed and plant morphology and agronomic features for two consecutive years. The transgenic lines containing Pi54 gene have higher tiller number, grain weight, epicotyl length, and yield compared to the non-transgenic control. Multivariate correlation analysis shows that blast resistance was positively correlated with the number of tillers; thousand grain weight and epicotyl length. These results will facilitate precise utilization of Pi54 gene and its orthologue in breeding programs for the development of rice cultivars with broad spectrum and durable resistance to M. oryzae.

Samter's triad with aural involvement: a novel approach to management.

BACKGROUND: Samter's triad is a well described condition manifesting as chronic rhinosinusitis with nasal polyposis, asthma and aspirin intolerance in a non-atopic individual. The underlying mechanism is still to be fully elucidated. However, aural disease has not been widely reported in these patients. In the few reported cases, most patients underwent major surgery with varying degrees of success. CASE REPORT: We report two Samter's triad patients with aural involvement. Both were successfully managed by conservative treatment, thus avoiding the need for major surgery. It appears that more Samter's triad patients may have aural disease than previously thought. CONCLUSION: We report good outcomes with conservative treatment, which is relevant because aural disease tends to reoccur in these patients.

Long-term quality-of-life outcomes in children undergoing adenotonsillectomy for obstructive sleep apnoea: a longitudinal study.

OBJECTIVES: To assess a cohort of patients who underwent adenotonsillectomy for obstructive sleep apnoea, 4 years after surgery for evidence of continued and long-term improvement in quality of life. We also sought to compare our results to Child Health Questionnaire scores obtained from our previous study. We also compared our data with a healthy UK children population from normative data available. DESIGN: Longitudinal study. SETTINGS: University Hospital Tertiary Referral Centre. PARTICIPANTS: A 4-year follow-up study of 37 children who underwent adenotonsillectomy for obstructive sleep apnoea confirmed on polysomnography. There were 19 boys and 18 girls from our initial cohort. The primary caregiver completed the validated Child Health Questionnaire Parental Form version-28, 4 years after initial surgery. Our control group consist of 221 healthy children aged 6-18 that were included as 'normal' controls in a study looking at children with juvenile arthritis. The children were defined as healthy by a physician and/or after declaration by the parent. MAIN OUTCOME MEASURE: Child Health Questionnaire Parental Form version-28 scores. RESULTS: A total of 33 patients (89%) from our initial cohort were contacted. The mean age was 10.6 (median, 11; range, 5-16). When compared with results obtained 3 months postoperatively, the mean scores were higher in five domains and were statistically significant in three subscales (Role Limitations P < 0.00001; Bodily Pain P < 0.002; and Global Health P < 0.02). There was a significant deterioration in Behaviour subscale (P < 0.0007) in spite of surgery. Compared with controls, 4-year follow-up scores were higher in five domains with the Global Health domain (P < 0.0004) being statistically significant. When the 4-year follow-up scores were compared with preoperative values, these were higher in all 13 domains with statistically significant improvements in nine domains, indicating that improvements had persisted 4 years after surgery. At 4 years, however, the means scores in many domains remain lower when compared with controls. CONCLUSION: Quality-of-life data are an important measure when deciding on a specific clinical intervention. In the short term, quality-of-life measures have been shown to improve after adenotonsillectomy for obstructive sleep apnoea. Our study demonstrates that the benefits of surgery are still persistent and the children continue to improve in the long term.

Improving tracheostomy care: a prospective study of the multidisciplinary approach.

OBJECTIVES: Suboptimal standards in tracheostomy care have been highlighted as a growing concern in view of the increasing demands for intensive care services. Our objective is to assess the impact of our model for tracheostomy care on patients with short-term tracheostomies (<4 months in situ) following their discharge from the intensive care unit. The model has three components: The St Mary's tracheostomy care bundle checklist, a dedicated tracheostomy multidisciplinary team and an educational programme. DESIGN: A 38-month prospective cohort study. SETTING: A London Teaching Hospital. PARTICIPANTS: A total of 102 patients with tracheostomy within the 19-month pre-intervention cohort and 95 patients in the 19-month post-intervention cohort. MAIN OUTCOME MEASURES: The number of clinical incidents, mean time taken for decannulation, mean total tracheostomy time and total number of days spent in the intensive care unit were assessed before and after the intervention. RESULTS: Time to decannulation following intensive care unit discharge decreased from 21 to 11 days, as did the mean total tracheostomy time, from 34 to 25 days (both statistically significant with a P < 0.0001 Mann-Whitney U-test). The number of critical incidents, which included all patients prior to exclusion, substantially declined following the introduction of intervention from 58 to 7 in the second year after intervention. CONCLUSIONS: A multidisciplinary care model significantly expedited the decannulation process and reduced the overall time that a tracheostomy was in situ. The intervention was associated with a reduction in clinical incidents and shorter intensive care unit admissions, which can be associated with significant monetary savings.