Quality-by-design-based microemulsion of disulfiram for repurposing in melanoma and breast cancer therapy.

Aim: The current study aims to develop and optimize microemulsions (ME) through Quality-by-Design (QbD) approach to improve the aqueous solubility and dissolution of poorly water-soluble drug disulfiram (DSF) for repurposing in melanoma and breast cancer therapy. Materials & methods: The ME was formulated using Cinnamon oil & Tween® 80, statistically optimized using a D-optimal mixture design-based QbD approach to develop the best ME with low vesicular size (Zavg) and polydispersity index (PDI). Results: The DSF-loaded optimized stable ME showed enhanced dissolution, in-vitro cytotoxicity and improved cellular uptake in B16F10 and MCF-7 cell lines compared with their unformulated free DSF. Conclusion: Our investigations suggested the potential of the statistically designed DSF-loaded optimized ME for repurposing melanoma and breast cancer therapy.

Identifying new medicinal uses of an existing marketed drug can save both money and time in the process of drug development. From many of the recently reported literature, disulfiram (a drug used for alcoholism) has shown its activity against various cancers, including breast and skin cancer. However, it possesses poor water solubility and absorption, leading to low medicinal activity. The current study aims to develop a novel microemulsion dosage form through a statistical design approach to enhance the solubility, dissolution and anticancer activity for repurposing in melanoma and breast cancer treatment. The novel microemulsion was prepared, statistically analyzed and optimized. The optimized microemulsion was found to be stable and showed improved medicinal activity against breast and skin cancer compared with the pure drug. Our research showed the potential of the developed microemulsion of the disulfiram for its new therapeutic use in skin cancer and breast cancer.

Efficacy and safety of monoamine reuptake inhibitors in attention deficit hyperactivity disorder: A Bayesian network meta-analysis.

The use of first-line drugs in clinical practice for attention deficit hyperactivity disorder (ADHD) is limited by their adverse effects. Many novel monoamine reuptake inhibitors (MRIs) with better safety profiles and comparable efficacy are also being tried for ADHD. This network meta-analysis (NMA) has evaluated the efficacy and safety of MRIs in ADHD. The data was extracted from 31 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases, and clinical trial registries. Quality assessment was performed using the risk of bias assessment tool (RoB2) by Cochrane Collaboration, and the random-effects model was used to estimate the effect size. Standardised mean difference (SMD) and 95% credible interval(95%CrI) were reported for the reduction in ADHD rating scale score. Network geometry was visualised, and node splitting was done for the closed triangles. Meta-regression was done for the duration of therapy. PRISMA-NMA guidelines were followed in selecting, analyzing, and reporting findings. The drugs showing significant reduction on the ADHD rating scale as compared to placebo are bupropion (SMD: 0.33; 95%CrI: 0.60,-0.059), dasotraline(SMD: 0.49; 95%CrI: 0.82,-0.16), venlafaxine(SMD: 0.71; 95%CrI: 1.3,-0.15), viloxazine(SMD: 0.45; 95%CrI: 0.77,-0.12). Other drugs (centanafadine, duloxetine, edivoxetine, reboxetine, tipepidine, vortioxetine) were no better than placebo in reducing symptom severity of ADHD. The efficacy of none of the drugs was found to be significantly different as compared to methylphenidate. Among all, duloxetine (OR:15; 95%CrI:1.8130) showed significantly more treatment-emergent adverse events than methylphenidate. In conclusion, venlafaxine, viloxazine, and bupropion are the most efficacious MRIs for ADHD symptom reduction as compared to placebo with high certainty of evidence.

Pharmacological interventions for antipsychotic-induced weight gain in schizophrenia: A network meta-analysis.

OBJECTIVE: Antipsychotic-induced weight gain (AIWG) is a significant but frequently neglected adverse effect of first- and second-generation antipsychotic therapy, which may lead to cardiovascular disturbances. The present network meta-analysis (NMA) was conducted to evaluate and compare the effects of available treatment options in antipsychotic-induced weight gain (AIWG). METHODS: The data was extracted from 68 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases and clinical trial registries. Random-effects Bayesian NMA was done to pool the effects across the interventions for the change in body weight from baseline. A network graph was built, a consistency model was run, node split analysis was performed, treatments were ranked as per the SUCRA score and meta-regression was done for the duration of therapy, baseline body weight and treatment strategy as the predictor variables. Finally, the results were sorted based on the certainty of evidence. RESULTS: The drugs showing significant reduction in body weight in order of magnitude of effect size include sibutramine 10 mg (-8.0 kg; -16. to -0.21), metformin 750 mg + lifestyle modification (-7.5 kg; -12 to -2.8), topiramate 200 mg (-7 kg; -10 to -3.4), metformin 750 mg (-5.7 kg; -9.3 to -2.1), topiramate 100 mg (-5.7 kg; -8.8 to -2.5), topiramate 50 mg (-5.2 kg; -10 to -0.57), liraglutide 1.8 mg (-5.2 kg; -10., -0.080), sibutramine 15 mg (-4.5 kg; -8.9 to -0.59), nizatidine 300 mg (-3.0 kg; -5.9 to -0.23) and metformin 1000 mg (-2.3 kg; -4.6 to -0.0046). There was no effect of duration of follow-up, baseline body weight and, preventive versus therapeutic strategy on weight reduction in AIWG. CONCLUSION: Metformin 750 mg with lifestyle modification was the most effective treatment for AIWG, followed by topiramate 200 mg, metformin 750 mg, and topiramate 100 mg with moderate certainty of evidence.

Repurposing of dextromethorphan as an adjunct therapy in patients with major depressive disorder: a randomised, group sequential adaptive design, controlled clinical trial protocol.

BACKGROUND: Therapeutic latency, lack of efficacy and adverse drug reactions are the major concerns in current antidepressant therapies. To overcome these treatment hurdles, add-on therapy to conventional antidepressant medications may lead to better therapeutic outcomes. The present randomised controlled trial has been planned to evaluate the efficacy and safety of add-on dextromethorphan to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD). METHODS AND ANALYSIS: A randomised, double-blind, add-on, placebo-controlled, group sequential design clinical trial will be conducted on patients with MDD who will be randomly assigned to the control and the test group in a 1:1 ratio. Patients in the test group will get dextromethorphan 30 mg once daily, whereas patients in the control group will receive a placebo once daily as an add-on to ongoing SSRI treatment for 8 weeks. All patients will be evaluated for the primary outcome (change in the Montgomery-Åsberg Depression Rating Scale score) and secondary outcomes (treatment response rate, remission rate, Clinical Global Impression, serum brain-derived neurotrophic factor, serum dextromethorphan and treatment-emergent adverse events) over the period of 8 weeks. Intention-to-treat analysis will be done for all parameters using suitable statistical tools. ETHICS AND DISSEMINATION: This study was approved by the Institutional Ethics Committee of All India Institute of Medical Sciences, Bhubaneswar, India, and the study conformed to the provisions of the Declaration of Helsinki and ICMR's ethical guidelines for biomedical research on human subjects (2017). Written informed consent will be obtained from the participants before recruitment. The results of this study will be published in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05181527.

Psychometric properties and factor structure of the suicidal narrative inventory in major depression: A multicentric evaluation.

BACKGROUND: The Suicidal Narrative Inventory (SNI) is a 38-item self-report measure developed to assess elements of the suicidal narrative, a subacute, predominantly cognitive, presuicidal construct. Our objectives were to assess the factor structure, validity, and reliability of the SNI-38 among adults with major depressive disorder (MDD). METHODS: Using a cross-sectional design, we administered the Hindi version of the SNI along with other self-report measures to adults with MDD, recruited from 24 tertiary care hospitals across India. Confirmatory factor analysis (CFA) was performed to assess the factor structure of SNI-38. Reliability (internal consistency) was assessed using Cronbach's alpha (α). Convergent, discriminant, and criterion validity of the SNI-38 were tested by comparing it against other appropriate measures. RESULTS: We collected usable responses from 654 Hindi-speaking participants (Mean age = 36.9 ± 11.9 years, 50.2% female). The eight-factor solution of the SNI showed good model fit indices (χ2[637] = 3345.58, p <.001, CFI =.98, and RMSEA =.08). Internal consistencies for the SNI subscale scores were good to excellent, α ranging from .73 to.92. While most subscales significantly converged with other measures, associations were comparatively weaker and inconsistent for the 'thwarted belongingness' and 'goal reengagement' subscales. CONCLUSION: Consistent with prior data, our study confirmed an eight-factor solution and demonstrated adequate psychometric properties for the Hindi version of the SNI-38 in our sample. These findings provide empirical support for the use of SNI to assess the suicidal narrative among Indian adults with MDD.

Nanovesicular ultraflexible invasomes and invasomal gel for transdermal delivery of phytopharmaceuticals.

Tweetable abstract Invasomes and invasomal gel are ultraflexible, soft vesicular, phospholipid based nanocarriers with deeper skin penetration ability for transdermal applications of drugs and phytopharmaceuticals.

Quality-by-design-based development of ultradeformable nanovesicular transgelosome of standardized Piper longum extract for melanoma.

Background: Melanoma is the most aggressive and deadly form of skin cancer. The stratum corneum of the skin is a major obstacle to dermal and transdermal drug delivery. Ultradeformable nanovesicular transferosome has the capacity for deeper skin penetration and its incorporation into hydrogel forms a transgelosome that has better skin permeability and patient compliance. Method: Here, the quality-by-design-based development and optimization of nanovesicular transgelosome of standardized Piper longum fruit ethanolic extract (PLFEE) for melanoma therapy are reported. Results: Compared with standardized PLFEE-loaded plain gel, the transgelosome displayed optimal pharmaceutical properties and improved ex vivo skin permeability and in vivo tumor regression in B16F10 melanoma-bearing C57BL/6 mice. Conclusion: The results reflect the potential of transgelosome for melanoma therapy.

Melanoma is a deadly form of skin cancer that originates from melanocytes in the skin. Skin is a major barrier to drug delivery. Transferosome is a liquid nanoformulation that has the capacity for deeper skin penetration. The transferosome was prepared from standardized Piper longum fruit ethanolic extract (PLFEE) and loaded into gel to form a transgelosome for improved skin application and patient compliance. Compared with extract-loaded plain gel, the transgelosome showed good pharmaceutical properties with better activity in melanoma (B16F10)-bearing female C57BL/6 mice. The therapeutic activity of the standard anticancer drug dacarbazine was improved with the prepared PLFEE transgelosome.

Efficacy and safety of tramadol in the treatment of opioid withdrawal: A meta-analysis of randomized controlled trials.

BACKGROUND: Pharmacotherapeutic options for the treatment of opioid withdrawal are limited by abuse potential, adverse effects, and lack of availability of existing drugs. The results from previous clinical trials on tramadol are contradictory and non-conclusive; hence the present meta-analysis was conducted to evaluate the efficacy and safety of tramadol in the treatment of opioid withdrawal. METHODS: Reviewers extracted data from eight relevant clinical trials after a literature search on MEDLINE/PubMed, Cochrane databases, and clinical trial registries. Quality assessment was done using the risk-of-bias assessment tool, and the random-effects model was used to estimate effect size in frequentist and Bayesian approaches. Subgroup analysis, meta-regression, and sensitivity analysis were done as applicable. PRISMA guidelines were followed in reporting findings. RESULTS: Tramadol significantly reduced opioid withdrawal scale score (SMD: -0.44; 95%CI: -0.76 to -0.13; PI: -1.54 to 0.71; p = 0.006) when all comparators were considered together in the frequentist approach but the reduction was non-significant in Bayesian approach. However, the subgroup analysis revealed no significant difference between tramadol and comparators like placebo (SMD: -1.12; 95%CI: -2.69 to 0.45) buprenorphine (SMD: -0.21; 95%CI: -0.43 to 0.01), clonidine (SMD: -0.26; 95%CI: -0.55 to 0.02) and methadone (SMD: -0.84; 95%CI: -1.78 to 0.10). Meta-regression showed non-significant associations between the SMD in opioid withdrawal score with the duration and dose of tramadol therapy. There were no significant differences in treatment retention at the end of studies between tramadol and comparators. Safety data in the individual studies were inadequate to analyze. CONCLUSION: Authors conclude that the efficacy of tramadol in reducing opioid withdrawal symptoms is not significantly different from comparators with low certainty of evidence against placebo, moderate against methadone, whereas with high certainty of evidence against buprenorphine and clonidine.

Quality by design-based development and optimization of fourth-generation ternary solid dispersion of standardized Piper longum extract for melanoma therapy.

The study aimed to enhance the solubility, dissolution, and oral bioavailability of standardized Piper longum fruits ethanolic extract (PLFEE) via fourth-generation ternary solid dispersion (SD) for melanoma therapy. With the use of solvent evaporation method, the standardized PLFEE was formulated into SD, optimized using Box-Wilson's central composite design (CCD), and evaluated for pharmaceutical performance and in vivo anticancer activity against melanoma (B16F10)-bearing C57BL/6 mice. The optimized SD showed good accelerated stability, high yield, drug content, and content uniformity for bioactive marker piperine (PIP). The X-ray diffraction (XRD), differential scanning calorimetry (DSC), polarized light microscopy (PLM), and selected area electron diffraction (SAED) analysis revealed its amorphous nature. The attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and high-performance thin layer chromatography (HPTLC) revealed the compatibility of excipients with the PLFEE. The contact angle measurement and in vitro dissolution study revealed excellent wetting of SD and improved dissolution profile as compared to the plain PLFEE. The in vivo oral bioavailability of SD reflected a significant (p < 0.05) improvement in bioavailability (Frel = 188.765%) as compared to plain extract. The in vivo tumor regression study revealed the improved therapeutic activity of SD as compared to plain PLFEE. Further, the SD also improved the anticancer activity of dacarbazine (DTIC) as an adjuvant therapy. The overall result revealed the potential of developed SD for melanoma therapy either alone or as an adjuvant therapy with DTIC.

Paroxysmal dystonia and psychotic exacerbations in chronic psychosis: Diagnostic dilemmas and preliminary treatment approaches.

Patients with chronic psychosis on prolonged antipsychotic therapy may present with paroxysmal dystonia along with an exacerbation of their psychotic symptoms: paroxysmal dystonia and psychotic exacerbations (PDPE). The interindividual variability in the clinical presentations of PDPE can pose challenges in its diagnosis and treatment. The objectives of this work are to (i) discuss this rare phenomenon through a series of 10 patients and a relevant literature review, (ii) conceptualize its neurobiological underpinnings, and (iii) explore the preliminary treatment approaches for its management. Acute stress and/or a dysfunctional gamma-aminobutyric acid (GABA) ergic or dopaminergic system may be implicated in the pathogenesis of PDPE. The episodes respond acutely to parenteral benzodiazepines, while long-term management can be achieved by reducing antipsychotic doses, switching to clozapine or using central GABA enhancers. This article is the first attempt at conceptualizing and exploring treatment options for the rare condition PDPE and intends to guide future research in this regard.

Bioengineered dual fluorescent carbon nano dots from Indian long pepper leaves for multifaceted environmental and health utilities.

In this article, we present the synthesis of Piper longum leaves-derived ethanolic carbon dots (PLECDs) using the most simplistic environmentally friendly solvothermal carbonization method. The PLECDs fluoresced pink color with maximum emission at 670 nm at 397 nm excitation. Additionally, the dried PLECDs dissolved in water showed green fluorescence with higher emission at 452 nm at 370 nm excitation. The UV spectra showed peaks in the UV region (271.25 nm and 320.79 nm) and a noticeable tail in the visible region, signifying the efficient synthesis of nano-sized carbon particles and the Mie scattering effect. Various functional groups (-OH, -N-H, -C-H, -C = C, -C-N, and -C-O) were identified using Fourier transform infrared spectroscopy (FTIR). Its nanocrystalline property was revealed by the sharp peaks in the X-ray diffraction (XRD). High-resolution transmission electron microscopy (HRTEM) photomicrograph displayed a roughly spherical structure with a mean size of 2.835 nm. The energy dispersive X-ray (EDAX) and X-ray photoelectron spectroscopy (XPS) revealed the elemental abundance of C, O, and N. The high-performance thin-layer chromatography (HPTLC) fingerprint of PLECDs showed an altered pattern than its precursor (Piper longum leaves ethanolic extract or PLLEE). The PLECDs sensed Cu2+ selectively with a limit of detection (LOD) and limit of quantification (LOQ) of 0.063 µM and 0.193 µM, respectively. It showed excellent cytotoxicity toward MDA-MB-231 (human breast cancer), SiHa (human cervical carcinoma), and B16F10 (murine melanoma) cell lines with excellent in vitro bioimaging outcomes. It also has free radical scavenging activity. The PLECDs also showed outstanding bacterial biocompatibility, pH-dependent fluorescence stability, photostability, physicochemical stability, and thermal stability.

Chemometric-Based Analysis of Metabolomics Studies of Bioactive Fractions of Pleurotus osteratus and Their Correlation with In Vitro Anti-Cancer Activity.

Richness in nutrients with an ample of the myco-bioactive molecules makes Pleurotus osteratus preferential mushroom. In this paper, we conducted a preliminary study on bio-assay-guided fractionation of dichloromethane:ethanol crude extract (1:1, v/v) of P. osteratus (CD) against human breast cancer cell line (MDA-MB-231). Later, CD and its potent hexane (H) and ethyl acetate (EA) fraction were screened against a panel of a human cancer cell lines. H fraction possesses higher cytotoxicity followed by EA and CD. Literature review revealed that polyphenol and ergosterol are the biomarkers found in P. osteratus and could responsible for its cytotoxic potential. Accordingly, hyphenated liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based polyphenol and ergosterol-targeted myco-metabolite profiling of CD, H, and EA fractions were carried out. Despite being significantly rich in polyphenol and ergosterol content, EA fraction showed moderate cytotoxicity. Considering this, liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF/MS)-based untargeted myco-metabolite profiling of CD, H and EA fractions was further conducted to identify a new biomarker. Tentatively, 20 myco-metabolites were identified, belonging to the class of steroids, alkaloid, terpenoid, fatty alcohol, and polyketide. The myco-metabolite variabilities among potent samples in correlation to their in vitro anti-cancer activity was explored using the different chemometric tools: principal component analysis (PCA), hierarchical clustering analysis (HCA), and partial least square (PLS). A probable synergistic action among identified myco-metabolites (betulin, solanocapsine, ophiobolin F, linoleoyl ethanolamide, (13R,14R)-7-labdene-13,14,15-triol, asterosterol, cholest-5-ene, (3b,6b,8a,12a)-8,12-epoxy-7(11)-eremophilene-6,8,12-trimethoxy-3-ol, beta-obscurine, myxalamid B, momordol, and avocadyne 4-acetate) may be responsible for the observed cytotoxicity potential of H fraction of P. osteratus.

Effect of regulated add-on sodium chloride intake on stabilization of serum lithium concentration in bipolar disorder: A randomized controlled trial.

OBJECTIVE: Lithium-induced natriuresis may lead to lithium retention and fluctuation of lithium levels during maintenance therapy. Therefore, the present study was conducted to evaluate the effect of add-on sodium chloride on serum lithium levels in bipolar disorder. METHODS: This RCT was conducted in 60 patients with type I bipolar disorder who were randomized into the control group that received lithium carbonate with the advice not to take additional salt (at the table) and the test group that received sachets of sodium chloride (1 g/d) as an add-on to lithium carbonate and were advised to restrict their additional salt intake (at the table) to 1 g/d. After baseline assessments, all patients were followed up at 4 weeks, 8 weeks, and 12 weeks when serum lithium, sodium, and potassium were estimated. Serum creatinine and aldosterone were repeated at 12 weeks. The percentage of patients showing fluctuations in serum lithium level (serum lithium <0.6 mEq/L or >0.8 mEq/L) was considered as the primary outcome measure. RESULTS: In the test group, the fluctuation rate in serum lithium (26.7%) was significantly (p = 0.01) lower than that in the control group (63.3%). Serum lithium values varied significantly across sampling times in the control group but not in the test group. There was a significant difference in serum lithium between the groups at 8 and 12 weeks of follow-up. There were no significant differences in the change in serum sodium, potassium, creatinine, aldosterone, creatinine clearance, and blood pressure within the group and between the groups. A significant positive correlation was found between serum lithium and aldosterone at baseline. CONCLUSIONS: Intake of add-on sodium chloride (1 gm/day) may reduce the fluctuations in serum lithium during the maintenance phase of lithium therapy in type I bipolar disorder. GOV IDENTIFIER: NCT04222816.

Tracing the Anti-cancer Mechanism of Pleurotus osteratus by the Integrative Approach of Network Pharmacology and Experimental Studies.

The present study identified the probable mechanism behind the anti-cancer activity of the hexane fraction of Pleurotus osteratus (HFPO) using network pharmacology and experimental validation. HFPO myco-metabolites targets and targets related to the cancer were mined from the online web server, and overlapping targets were screened. Out of the 74 overlapping targets, 33 targets were identified in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of cancer. Furthermore, the main active myco-metabolites and hub targets were identified by network analysis of the compound-targets network and protein-protein interaction (PPI), respectively. Molecular docking results showed good binding affinity of the hub targets with their respective myco-metabolites. HFPO induced in-vitro anti-cancer activity by affecting the PI3K-AKT-mTOR pathway, besides time-dependent cell cytotoxicity and apoptotic cell body formation. Additionally, tumor volume reduction was observed in HFPO-treated Ehrlich ascites carcinoma (EAC) bearing Swiss albino mice. Overall, HFPO induces anti-cancer potential by modulating the PI3K-AKT-mTOR signaling pathway.

A multicentric exploratory study of behavioral and psychological symptom characteristics of dementia.

Background: Behavioral and psychological symptoms (BPS) are usually the expected consequences of dementia. BPS increases morbidity and burden, affects the quality of life, and impacts care costs. However, the symptom characteristics, clinical correlations, and symptom-specific clusters aiding the diagnosis are less well studied, especially in the Indian population. Materials and Methods: The present study examined the BPS clusters based on various cognitive and neuropsychiatric profiles in patients with dementia under a multicentric study in India. We did a cross-sectional assessment using the Neuropsychiatric Inventory Questionnaire (NPI-Q) and cognitive functions by Montreal Cognitive Assessment (MoCA), and the severity of dementia using the Clinical Dementia Rating (CDR) scale. In addition, all of the participants were evaluated on a structured Clinical Interview for DSM-5 Research Version for past or current psychiatric disorder(s). Results: We describe the various BPS clusters uniquely associated with the severity of dementia. Further, on linear regression analysis, we predicted three symptom clusters (anxiety, irritability, aberrant motor) in mild, two symptom clusters (disinhibition, agitation/aggression) in moderate and three symptom clusters (delusion, euphoria/elation, disinhibition) in severe dementia. Conclusion: The study provides insights into the various symptom characteristics and inter-relationship of BPS, which may benefit the clinician while assessing patients with dementia.

Comparison of Acute Followed by Maintenance ECT vs Clozapine on Psychopathology and Regional Cerebral Blood Flow in Treatment-Resistant Schizophrenia: A Randomized Controlled Trial.

BACKGROUND AND HYPOTHESIS: In treatment-resistant schizophrenia (TRS), Clozapine is only approved treatment with undesirable side-effects, warranting better alternatives. Our hypothesis is acute followed by maintenance Electroconvulsive Therapy (M-ECT) will be comparable in efficacy and safety to Clozapine in TRS. STUDY DESIGN: In this open-label trial, 60 TRS patients were randomized equally to M-ECT (following an acute-course) or Clozapine. Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Schizophrenia Scale (CGI-SCH), Montreal Cognitive Assessment (MoCA), and Global assessment of functioning (GAF) were measured and compared within and between the groups at baseline, 6 weeks, 12 weeks, and 24 weeks. SPECT-CT brain was done at baseline and 24 weeks to compare the changes in regional cerebral perfusion between the groups and correlate with the changes in the outcome-measures. STUDY RESULTS: The PANSS-T scores changes from baseline over the observation-points were significant in both M-ECT and clozapine groups (P < .001), with comparatively better reduction with M-ECT (P < .001). Similar trends were observed in PANSS subscales, CGI-SCH and GAF in both groups, with significantly better improvement with M-ECT over the study-period. After 24 weeks, there was significantly better perfusion with M-ECT in bilateral prefrontal and temporal cortices (P < .05). With M-ECT, a positive correlation was found between changes in PANSS-P scores and left-lateral Temporal cortical perfusion (r = .465, P = .017). CONCLUSIONS: Acute followed by M-ECT was more effective than clozapine over 6 months in reducing the positive and negative symptoms, general psychopathology, illness-severity, and improving the global functionality in TRS [clinicaltrials.gov: NCT03807882].

Tinospora cordifolia Leaves Derived Carbon dots for Cancer Cell Bioimaging, Free radical Scavenging, and Fe3+ Sensing Applications.

Herein, we report the fabrication of Tinospora cordifolia leaves-derived carbon dots (TCLCDs) from aqueous extract of leaves as carbon source via simple, environmentally friendly, hydrothermal carbonization (HTC) technique. The synthesized TCLCDs were characterized for their physicochemical properties and further explored for in-vitro cancer cell bioimaging, radical scavenging, and metal ion sensing. The synthesized TCLCDs showed excitation-dependent emission property with maximum emission at 435 nm under the excitation of 350 nm. The High-Resolution Transmission Electron Microscopy (HRTEM) results revealed a roughly spherical shape with an average diameter of 5.47 nm. The diffused ring pattern of Selected Area Electron Diffraction (SAED) and halo diffraction pattern of X-ray diffraction (XRD) disclosed their amorphous nature. The Energy Dispersive X-ray (EDX) showed the existence of C, N, and O. The Fourier-transform infrared spectroscopy (FTIR) revealed the presence of -OH, -NH, -CN, and -CH groups. The TCLCDs showed excellent cellular biocompatibility with dose-dependent bioimaging results in melanoma (B16F10) and cervical cancer (SiHa) cell lines. Also, they exhibited excellent scavenging of free radicals with an IC50 value of 0.524 mg/mL & selective Fe3+ ion sensing with a detection limit of 0.414 µM. Further, they exerted excellent bacterial biocompatibility, photostability, and thermal stability. The overall results reflected their potential for in-vitro cancer cell bioimaging, free radical scavenging, and selective Fe3+ ion sensing.