A formal vinylic substitution reaction for the synthesis of α,ß-unsaturated enol esters and their anticancer potential.

Arylsulfonyl group-bearing α,ß-unsaturated enol esters were readily assembled via the Cs2CO3-mediated union of 2-bromoallyl sulfones and cinnamic acids. The overall transformation is equivalent to an sp2 carbon-oxygen coupling reaction, and therefore constitutes a formal vinylic substitution. Several of the products display promising levels of antiproliferative activities higher than that of the anticancer drug carboplatin. Thiophenol reacted with 2-bromoallyl sulfones under identical conditions to afford α-thiophenyl-α'-tosyl acetone via an apparent aerial oxidation.

Optimization of vacuum impregnated nutmeg rind candy using RSM modeling: effect on functional and nutritional properties.

Vacuum impregnation (VI) stands as an innovative technique, used to create novel food formulations by impregnating vital nutritive compounds into natural food matrices. Process variables were syrup temperature ranging from (50 to 70 °C), syrup concentration (60° to 80° Brix), and VI duration (10 to 20 min). The optimal conditions emerged at 66.81 °C for syrup temperature, 71.58° Brix for syrup concentration, and a precise 11.59 min for the VI duration. At these paramount conditions, the candy exhibited striking attributes such as 50.0% water loss, 12.23% sugar gain, chewiness of 9 N, and lightness value of 22.17. The predicted values using the developed model were validated with experimental data and indicated the adequacy of the generated model. The functional characterization of the optimized nutmeg rind candy showcased a marked reduction in myristicin content, signifying an augmented level of safety for consumption. Furthermore in-vitro anti-bacterial assay, total phenolics, flavonoids and tannin content, anti-oxidant potential, proximate composition and microstructure of the optimized candy were analysed.

A study of [2 + 2] cycloaddition-retroelectrocyclization in water: observation of substrate-driven transient-nanoreactor-induced new reactivity.

Organic solvents limit [2 + 2] cycloaddition-retroelectrocyclization (CA-RE) in biological fields. We examined the formation of 1,1,4,4-tetracyanobuta-1,3-dienes (TCBDs) through CA-RE reactions and their unusual reactivity to produce N-heterocyclic compounds when the nature of the surfactant and the concentrations were varied in the aqueous phase. An environment in which transient self-assemblies (vesicles) were induced by the substrate and surfactant molecules initiated new reactivity through H2O addition on the TCBD, generating the enol form of the intermediate, which results in the formation of the 6,6-dicyano-heteropentafulvene (amidofulvene) compound, while lamellar sheets at higher concentrations favored TCBD generation. Interestingly, the amidofulvene underwent a clean transformation to 6-membered heterocycles that resemble cardiotonic drugs (milrinone, amrinone) via keto-enol tautomerism mediated by a polar aprotic solvent, opening up a new avenue for drug discovery. Unlike organic-solvent-mediated CA-RE reactions, the present nanoreactor-mediated approach enabled the selective production of TCBDs as well as new heterocycles using H2O as a green solvent. In addition to the widely explored organic electronics/materials, we believe that this study will help to overcome the long-standing limitation of CA-RE reaction applicability in biological fields.

A systematic study to unravel the potential of using polysaccharides based organic-nanoparticles versus hybrid-nanoparticles for pesticide delivery.

To daze conventional pesticide release limitations, nanotechnology-mediated pesticide delivery using natural polymers has been actively investigated. However, the lack of information on what are the beneficial/non-beneficial aspects of using hybrid- and organic-nanoparticles (NP) and among the polysaccharides which are better suited concerning pesticide loading efficiency (PLE wt%), entrapment efficiency, and sustained pesticide release (SPR %) has prompted us to investigate this study. In this report, we systematically investigated a series of polysaccharides such as starch (S), cellulose (C), aminocellulose (AC), and sodium carboxymethylcellulose (NaCMC) coated on magnetite NP (MNP, Fe3O4) and complete organic nanocarrier systems (starch and cellulose) that have no MNP part were compared for the PLE wt% and SPR % efficiencies for chlorpyrifos (ChP) insecticide. Overall, all nanocarriers (NCs) have shown good to excellent PLE wt% due to the smaller-sized NP obtained through optimal conditions. However, among the hybrid polysaccharides studied, starch MNP has shown a maximum PLE of 111 wt% in comparison with other polysaccharides (80-94 wt%) coated hybrid-NCs as well as with organic-NCs (81-87 wt%). The use of inorganic support does improve the PLE wt% markedly for starch but not for cellulose derivatives. Similarly, the SPR results of S-NP showed a remarkably better sustained release profile for ChP of 88% in 14 d. In contrast, other unfunctionalized and functionalized celluloses exhibited poor release profiles of 60%-20% for the same period. This study may help the researchers choose the right system for designing and achieving enhanced pesticide efficiency.

Role of Pirfenidone in Idiopathic Pulmonary Fibrosis - A Longitudinal Cohort Study.

BACKGROUND: But so far there is no proven pharmacological treatment for Idiopathic pulmonary fibrosis (IPF). As trials investigating different agents with different mechanisms of actions are going on, encouraging results have led to the licensing of the first IPF-specific drug, Pirfenidone. OBJECTIVE: To assess the proportion of IPF among interstitial lung disease patients and to assess their treatment response to Pirfenidone. MATERIAL AND METHODS: All consecutive patients attending the outpatient department from 1st January 2012 to 30th June 2012 with a proven diagnosis of Interstitial lung Disease (ILD) were included in this longitudinal cohort study. Out of the total ILDs, patients with IPF were identified. The disease, its natural course, available treatment options and the risks and benefits of drugs were discussed with each IPF patient along with their family members. After obtaining their consent, we started 23 patients on a combination of Pirfenidone, N-acetyl cysteine (NAC) and proton pump inhibitors (PPI). Patients were followed up for 52 weeks. Pirfenidone was discontinued in one patient due to an adverse effect 1 month after onset of treatment. Anova test using SPSS software and independent T test was used to analyse the data. RESULTS: During the study period 69 patients with ILD attended our OPD which included 24 IPF patients representing 34.8% and 23 of these patients received treatment with Pirfenidone, NAC and PPI. One patient discontinued Pirfenidone due to adverse effects. After 12 months, 8 patients had worsening of FVC ≥10%, the FVC of 7 patients remained stable, 8 patients could not repeat the tests and none of them had improvement. There was less than 15% decline in DLCO for 9 patients, 7 patients could not repeat the test and none improved. 8 patients had stable dyspnoea on exertion and 11 had worsening. Three patients died. Combining all the above parameters, only 4 patients had stable disease with the rest having no improvement. CONCLUSIONS: The present study does not show any significant beneficial effect for Pirfenidone. Only four patients remained stable which cannot be attributed to the effect of any particular management strategy.

Biocidal polymer derived near white light-emitting polymeric carbon particles for antibacterial and bioimaging applications.

A growing antimicrobial crisis has increased demand for antimicrobial materials. It has become increasingly popular to convert polymeric macromolecules into polymeric carbon particles (PCP) in order to achieve highly biocompatible materials with unique properties as a result of the ability to synthesize nanomaterials of the right size and add value to existing stable polymers. This work presents the tuning of PCP for antibacterial application by combining a biocidal polymer with one-pot solvothermal synthesis. PCP displayed broad-spectrum antibacterial activity via various mechanisms, including inhibition of bacterial cell walls, ROS generation, and antibiotic resistance. Furthermore, these biocidal PCP were observed to show excitation-independent near-white light emission which on the other hand is generally possible due to mixed sizes, doping, and surface effects. As opposed to the parent biocidal polymer, PCP added ROS-mediated bactericidal activity, increased cytocompatibility, and nanofibers with anti-adhesive effects and potential of imaging bacterial cells.

Evaluation of microplastic pollution and risk assessment in a tropical monsoonal estuary, with special emphasis on contamination in jellyfish.

Estuaries, which serve as vital links between land and coastal ecosystems, play a significant part in facilitating the transfer of plastic waste from the land to the ocean. In this research, we examined the prevalence, characteristics, and ecological risks of microplastics (MPs) in the extensively urbanized Cochin Estuarine System (CES), India. Additionally, it represents one of the initial evidence-based examinations of MPs ingestion by jellyfish in Indian waters, focusing on Acromitus flagellatus, Blackfordia virginica, and Pleurobrachia pileus species. The abundance of MPs found in the surface water of the Cochin Estuarine System (CES) varied between 14.44 ± 9 to 30 ± 15.94 MP/m3, with an average of 21.6 ± 11 MP/m3. In both surface waters and jellyfish from the Cochin Estuarine System (CES), fibers were the most prevalent type of MPs, with polyethylene (PE), polypropylene (PP), and polyamide (PA) being the most common polymer varieties. To evaluate the current levels of MPs and their effect on the CES, the Pollution Load Index (PLI), Potential Ecological Risk Index (PERI), and Polymeric Risk Index (H) were utilized. The high PLIestuary values (20.33), high Hestuary values (234.02), and extreme PERIestuary value (1646.06) indicate that the CES is facing an extreme ecological risk. Among the 280 jellyfish individuals examined, 118 (42.14%) were recognized to contain MPs with an average of 1.54 ± 2.68 MPs/individual. Pearson bivariate analysis revealed a significant correlation between the jellyfish bell size and number of plastics per individual. Comparison between jellyfish species revealed, the majority (66%) of the MPs identified in jellyfish were from A. flagellatus and 44 among the 50 jellyfish examined (88%) had MPs. These findings suggest that A. flagellatus may be a potential sink for MPs and may be utilized to be a bioindicator for monitoring MPs contamination in estuarine systems, aiding in future plastic pollution mitigation efforts.

Patterns and variability in the microplastic contamination along the southwest coast of India with emphasis on submarine groundwater discharge sites.

Beach sediments of the southwest coast of India were analysed to estimate the microplastic contamination with emphasis on the submarine groundwater discharge (SGD) zones. Both SGD and non-SGD sites were assessed for abundance, morphotype and polymer type of microplastics. Microplastic load was 230.429 ± 62.87 particles per 100 g. Fibre, mainly blue, was the abundant morphotype, followed by fragment, foam and film. The polymer types were POLYETHYLENE (PE) (30.77 %), POLYPROPYLENE (PP) (26.92 %), POLYAMIDE (PA) (19.23 %), POLYSTYRENE (PS) (11.54 %), ETHYLENE VINYL ACETATE (EVA) (7.692 %) and POLYVINYL CHLORIDE (PVC) (3.846 %). The SGD zones exhibited higher microplastic contamination with statistically significant variations from non SGD sites. The study accounts the levels of microplastic contamination along the southwest coast of India, a major fishery zone. The higher abundance of microplastic in the SGD zones indicates the significance of subterranean groundwater through flow as a pathway of anthropogenic contaminants towards marine ecosystems.

External Ear Anomalies and Minor Physical Anomalies in Depressive Disorder Patients and Healthy Controls.

Objective: To determine if external ear anomalies (EEAs) and minor physical anomalies (MPAs) are more prevalent in patients with depressive disorder than in healthy controls.Methods: This cross-sectional study was conducted at a tertiary-level referral center between October 1, 2019, and September 30, 2020, and included 100 patients with depressive disorder (diagnosed per ICD-10 criteria) and 100 aged- and sex-matched healthy controls. The study participants were examined using the External Ear Anomalies Assessment Scale and the extended Waldrop Scale.Results: Independent samples Mann-Whitney U test showed a higher prevalence of mean EEAs and MPAs in patients with depressive disorder. Adherent ear lobe was the most common ear anomaly in both patients (52%) and controls (41%), followed by Darwinian tubercle (21% in the patient group and 19% in the control group).Conclusions: External ear anomalies are more prevalent in patients with depressive disorder, supporting the neurodevelopmental theory of depression. These EEAs need further description and attention for possible inclusion in scales that assess minor physical anomalies and may be used as an endophenotypic marker for depression in the future.Prim Care Companion CNS Disord. 2023;25(4):22m03416. Author affiliations are listed at the end of this article.

Cognitive impairment in 'non-user' first-degree relatives of persons with cannabis dependence syndrome: A pilot, endophenotype study.

INTRODUCTION: Cannabis use disorders are global emerging problem nowadays, with high prevalence and morbidity. Cognitive impairments, and also corresponding genetic vulnerability, has been fairly replicated in individuals with cannabis dependence. However, there are few studies that assess cognitive functioning as an endophenotype or a trait marker for cannabis dependence. While the primary objective of this study was to assess the endophenotype pattern of cognitive dysfunction in cannabis dependence, assessing the association between the degree of cognitive functioning, and their socio-demographic and clinical variables in the cannabis dependence patients and their first-degree relatives was the secondary objective. METHODOLOGY: We compared cognitive functioning across three groups- patients with cannabis dependence syndrome, their 'non-user' first-degree relatives and healthy controls, with 30 participants in each group. Five cognitive domains- attention and concentration, verbal fluency, memory, visuospatial ability and executive functions were assessed. We assessed for endophenotype pattern of statistical significance in pairwise analyses of Kruskal-Wallis test, which was corrected for multiple comparisons. Subsequently, correlation analysis to assess association of cognitive impairment with socio-demographic and clinical variables was conducted. RESULTS: Although impairment in attention and executive functions also was seen in patients with cannabis dependence, endophenotype pattern of statistical significance in pairwise analyses, with impairment in first-degree relatives too, was seen in all sub-scores of verbal fluency and verbal memory. None of the correlations were significant. CONCLUSION: 'Non-user' first-degree relatives of patients with cannabis dependence too show significant cognitive impairment. Verbal fluency and verbal memory are possible endophenotypes or trait markers for cannabis dependence syndrome.

Targeted treatment of invasive fungal infections accelerates healing of foot wounds in patients with Type 2 diabetes.

AIM: To test the hypothesis that fluconazole plus standard care is superior to the standard care for diabetic foot wounds infected with deep-seated fungal infections. METHODS: We carried out a randomized, controlled, open-label, parallel-arm study in 75 patients with both fungal and bacterial infections in deep tissues of diabetic foot wounds. Thirty-seven patients (control group) were given standard care (surgical debridement + culture-specific antibiotics + offloading + glycaemic control) and 38 patients (treatment group) were given fluconazole 150 mg daily plus standard care. Wound surface area was measured every 2 weeks until the endpoints (complete epithelialization or skin grafting) were met. RESULTS: By week 4, the mean wound surface area reduced to 27.3 from 111.5 cm(2) in the treatment group, as opposed to 67.1 from 87.3 cm(2) in the control group. Subsequently, the mean wound surface areas were remarkably smaller in the treatment group compared with the control group, and statistically significant differences (P ≤ 0.05) in mean wound surface area were observed between the treatment group and the control group at week 6. However, no statistically significant (P ≤ 0.47) difference in complete healing was observed between the treatment group and the control group, 20 vs. 24. The mean wound healing time for the treatment group was 7.3 weeks, whereas for the control group it was 11.3 weeks (P ≤ 0.022). Similarly, the probability of wound healing in the treatment group was 50 vs. 20% in the control group at week 10. CONCLUSIONS: Fluconazole plus standard care was superior to standard care alone in accelerating wound reduction among patients with diabetes with deep-seated fungal infections in diabetic foot wounds. Those in the treatment group who did heal, healed more quickly (P ≤ 0.022), but overall healing was not different.

"Esketamine" in Borderline Personality Disorder: A Look Beyond Suicidality.

Borderline personality disorder (BPD) is an extremely disabling condition that affects almost every dimension of a patient's life. The S-enantiomer of ketamine (esketamine) was approved by the Food and Drug Administration (FDA) in 2019 in conjunction with an oral antidepressant for the management of treatment-resistant depression (TRD) in adults. Our patient is a 27-year-old female with a long-standing diagnosis of BPD and treatment-resistant major depressive disorder (MDD) who presented to a tertiary care hospital after a baleful suicide attempt. As per treatment guidelines, "esketamine" intranasal spray in conjunction with citalopram 20 mg was started in the outpatient setting at a dose of 56 mg twice weekly for four weeks, followed by 56 mg once weekly, which was further titrated to 84 mg once weekly. Two years into treatment, the patient and her mother report around 70% improvement in her depression and anxiety with around 80% improvement in her behavioral symptoms. Esketamine's potential action on patients with BPD can be partially explained by its very well-documented effect on the glutamate receptor antagonism. Additionally, patients with stress-induced suicidal ideations (SI), which are seen in borderline patients, are better responsive to ketamine. In conclusion, we recommend a trial of intranasal esketamine in patients with BPD with treatment-resistant MDD and frequent episodes of self-harm. Treatment with esketamine could potentially reduce the number of emergency room visits for impulsive suicide attempts and help reduce the life burden of BPD and its impact on family members.

Tuning of cross-Glaser products mediated by substrate-catalyst polymeric backbone interactions.

Tuning of cross-Glaser products using different polymeric backbones supported by copper oxide nano-catalysts has been demonstrated by tweaking the substrate-catalyst interactions under greener conditions. Further, highly reactive magnetically separable and recyclable catalyst with scalability is demonstrated.

Self care integrative treatment demonstrated in rural community setting improves health related quality of life of lymphatic filariasis patients in endemic villages.

This study assessed impact of community based self care integrative treatment provided through mass camps in villages of three districts of Kerala, India endemic for lymphatic filariasis (LF). Two most endemic Primary Health centres (PHCs) were selected from each of the three districts, where maximum concentration of LF patients is recorded. Fourteen one day LF camps, each attended by 30-40 patients were conducted. Trained Accredited Social Health Activists encouraged LF patients to attend camps. Skin wash and drying, care of bacterial entry points using dermatology drugs, and simple yoga and breathing exercises were demonstrated in these camps. Patients were advised to continue these self care activities daily at home for six months. The quality of life (QoL) of LF patients was determined for Indian life style domains using validated and pretested specific questionnaire (LF-specific QoL questionnaire-LFSQQ). It addressed conditions and state of individuals with reference to LF. The questionnaire had 7 domains and each domain consisted of a series of questions with likert scale (no problem, mild, moderate, severe, most severe). 446 patients attended one day camps to get training on integrative self care treatment. 425 patients (95.3%) were followed up after six months and QoL was reassessed. Each patient's QoL in mobility, self care, usual activity, pain and discomfort and social relationship significantly improved (P value <0.01). Psychological health showed no significant change. The disease burden, for the purpose of the study was measured by asking questions about history of painful redness, swelling and cellulitis of legs (filarial fever), foul smell (odor), itching (eczema/discharge from limb), wound (non healing ulcer) and weight/size of the limb. The difference in disease burden as recorded during the sixth month follow up was measured using dependent t test, reduced significantly (P value <0.01) in 409 (96.2%) patients. 103 (24.2%) patients experienced fever during follow up. Severity of inflammatory episodes reduced from severe problem to no problem, after six months of home based self care. There was significant relation between treatment regularity and QoL status (P value=0.003). The community based one day camps that trained LF patients on skin care and daily yoga and breathing practices improved QoL.