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Cerebellum plays an important role in speech motor control. Various tasks like sustained phonation, diadochokinesis and conversation have been used to tap the speech timing abilities of dysarthric clients with cerebellar lesion. It has recently been proposed that not all areas of the cerebellum may be involved in speech motor control; especially aspects concerned with timing of speech events. In the present study, the timing of articulatory movements in three clients with lesions restricted to different cerebellar loci was investigated. A relational speech timing paradigm was used to investigate initial syllable vowel duration (ISVD) in these three clients. The findings were compared with 15 age and gender matched controls. The results suggest that subjects with cerebellar right hemispheric cerebellar lesion showed reduced preservation of relational timing measures as compared to cerebellar vermis lesion i.e. midline structures and cerebellar left cerebellar hemispheric lesion, thus indirectly suggesting a differential loci specific control in cerebellum for relational speech timing. [ABSTRACT FROM AUTHOR]

The catenin p120 (p120ctn) is an armadillo repeat domain protein that binds to cadherins and has been shown to facilitate strong cell-cell adhesion. We have investigated a possible link between heterotrimeric G proteins and p120ctn, and found that both Gα12 and Gα13 can completely and selectively abrogate the p120ctn induced branching phenotype in different cell types. Consistent with these observations, the expression of Gα12 or Gα13 compensates for the reduction of Rho activity induced by p120ctn. On the other hand, p120ctn can be selectively coimmunoprecipitated with Gα120ctn, and the coimmunoprecipitation was favored by activation of the G protein. A specific interaction between p120ctn and Gα12Q231L was also observed in in vitro binding experiments. In addition, p120ctn can be immunoprecipitated along with GGα12Q231L in L cells in absence of E-cadherin. Interestingly, the expression of GGα12Q231L increases the amount of p120ctn associated with E-cadherin. These findings demonstrate that G&apha;12 and p120ctn are binding partners, and they also suggest a role for Gα12 in regulating p120ctn activity and its interaction with cadherins. We propose that the Gα12-p120ctn interaction acts as a molecular switch, which regulates cadherin-mediated cell-cell adhesion. [ABSTRACT FROM AUTHOR]

Delayed recovery/awakening/ emergence can occur under anaesthesia and is multifactorial, could be drug or non drug related. Similarly, we report a case of delayed recovery in a 68-year-old patient, for laparoscopic cholecystectomy, a known case of hypertension, bronchial asthma and hypothyroidism. Preoperatively, she was optimised for her medical disorders; however, she had delayed recovery from general anaesthesia. The delayed recovery, often, would be expected in a case of hypothyroidism, however in our patient it was found to be associated with inadvertent hypokalemia. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Anesthetic management of a patient with Montgomery t-tube in situ for direct laryngoscopy" published in the previous issue.

The article reports on a man who had a routine cardiac evaluation. It says that the patient has chosen a computed tomography (CT) angiogram (CTA) of the coronary arteries, revealing an anomalous right coronary artery (RCA) originating from the left coronary sinus and coursing between the aortic and main pulmonary artery. Accordingly, coronary artery anomalies appear in around 1% of patients undergoing cardiac catheterization.

Drug discovery is a complex and multifaceted process aimed at identifying new therapeutic compounds with the potential to treat various diseases. Traditional methods of drug discovery are often time-consuming, expensive, and characterized by low success rates. Because of this, there is an urgent need to improve the drug development process using new technologies. The integration of the current state-of-art of artificial intelligence (AI) and machine learning (ML) approaches with conventional methods will enhance the efficiency and effectiveness of pharmaceutical research. This review highlights the transformative impact of AI and ML in drug discovery, discussing current applications, challenges, and future directions in harnessing these technologies to accelerate the development of innovative therapeutics. We have discussed the latest developments in AI and ML technologies to streamline several stages of drug discovery, from target identification and validation to lead optimization and preclinical studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: Ethical committee approval is not applicable. Human and animal rights: This study does not contain any studies with animal performed by any of the author. Informed consent from patient: Prior Informed Consent has been provided by the patient.

Resistance to shattering is essential for seed production in domesticated crops. In a recent study, Li et al. found that this trait arose in soybean through mutations in two genes, Shattering1 (Sh1) and Pod dehiscence1 (Pdh1), within a single quantitative trait locus (QTL). Sh1 reduces fiber cap cell wall thickness, while Pdh1 regulates lignin distribution. These genes could be valuable targets for breeding shattering-resistant crops., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Acute myeloid leukemia (AML) is one of the leading leukemic malignancies in adults. The heterogeneity of the disease makes the diagnosis and treatment extremely difficult. With the advent of next-generation sequencing (NGS) technologies, exploration at the molecular level for the identification of biomarkers and drug targets has been the focus for the researchers to come up with novel therapies for better prognosis and survival outcomes of AML patients. However, the huge amount of data from NGS platforms requires a comprehensive AML platform to streamline literature mining efforts and save time. To facilitate this, we developed AMLdb, an interactive multi-omics platform that allows users to query, visualize, retrieve, and analyse AML related multi-omics data. AMLdb contains 86 datasets for gene expression profiles, 15 datasets for methylation profiles, CRISPR-Cas9 knockout screens of 26 AML cell lines, sensitivity of 26 AML cell lines to 288 drugs, mutations in 41 unique genes in 23 AML cell lines, and information on 41 experimentally validated biomarkers. In this study, we have reported five genes, i.e. CBFB, ENO1, IMPDH2, SEPHS2, and MYH9 identified via our analysis using AMLdb. ENO1 is uniquely identified gene which requires further investigation as a novel potential target while other reported genes have been previously confirmed as targets through experimental studies. Top of form we believe that these findings utilizing AMLdb can make it an invaluable resource to accelerate the development of effective therapies for AML and assisting the research community in advancing their understanding of AML pathogenesis. AMLdb is freely available at https://project.iith.ac.in/cgntlab/amldb., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Abstract The identification of individuals with the greatest risk of progression to active tuberculosis (TB) disease from the huge reservoir of Mycobacterium tuberculosis ( Mtb ) infected individuals continues to remain an arduous ascent in the global effort to control TB. In a two-year prospective study, we analysed metabolic profiles in the unstimulated and TB antigen stimulated QuantiFERON supernatants of 14 household contacts (HHCs) who progressed to TB (Progressors) and 14 HHCs who remained healthy (Non-Progressors). We identified 21 significantly dysregulated metabolites in the TB antigen-stimulated QuantiFERON supernatants of Progressors, of which the combination of Malic acid and N-Arachidonoylglycine had maximum AUC of 0.99. Eighteen significantly dysregulated metabolites were identified in the unstimulated QuantiFERON supernatants of Progressors, among which the combination of Orotic acid and the phosphatidylcholines PC (O-34:1), PC (O-18:1(9Z)/16:0), PC (O-18:1(11Z)/16:0) had the maximum AUC of 0.98. Most of the dysregulated metabolites belonged to the pathways of fatty acid metabolism, lipid metabolism and nitric oxide metabolism. Validation of these metabolic signatures in large, diverse cohorts would pave way for targetted intervention of TB disease.

Patients with undiagnosed and/or rare disorders frequently manifest dysmorphic and neurological features. There is a lack of information on the effectiveness of telehealth in the evaluation of these disorders. We thus compared an unassisted virtual physical examination (PE) with an in-person PE in undiagnosed individuals and also assessed participant telehealth satisfaction. Twenty-six individuals enrolled in the Undiagnosed Diseases Network study underwent an in-home synchronous virtual PE, and a subsequent in-person PE, by the same clinician. The participants completed surveys on telehealth usability and provider empathy. On PE, general appearance and craniofacial features showed near perfect agreement (κ = 0.81-1.00) between the telehealth and in-person evaluations. Specific components of the neurological examination demonstrated substantial agreement (speech, gait, coordination; κ > 0.61), whereas others had moderate agreement (muscle tone, strength; κ = 0.41-0.60), and a few had none to slight agreement (skin; κ < 0.20). Some systems could not be examined in the virtual PE. Importantly, features relevant to diagnosis or management were missed on the virtual PE in only 2/26 individuals. The participants were satisfied with the quality of the telehealth interaction, as well as empathy demonstrated by providers in the virtual interface. Telehealth is effective for PEs in undiagnosed diseases and is acceptable to affected individuals., (© 2024 Wiley Periodicals LLC.)

One of the key challenges in medical research is developing safe medications to treat neurodegenerative disorders. Increased oxidative stress, mitochondrial dysfunction, and neuroinflammation are common features of Alzheimer's disease (AD) and Parkinson's disease (PD). Silent information regulator 1 (SIRT-1), part of the sirtuin family, plays a critical role in various physiological processes by binding to histones and nonhistone proteins. SIRT-1 primarily mitigates oxidative stress and regulates mitochondrial activity by maintaining the deacetylated form of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), ensuring stable PGC-1α levels. Research has shown reduced SIRT-1/PGC-1α expression in AD and PD models. Targeting this pathway presents a promising therapeutic approach for managing AD and PD, potentially leading to disease-modifying treatments and improved outcomes. This review highlights the findings of various studies suggesting that the SIRT-1/PGC-1α pathway promotes mitochondrial biogenesis, synaptic plasticity, and cognitive function, as well as exerts antioxidant, anti-inflammatory, and anti-apoptotic effects, offering a potential method for AD and PD treatment., (© 2024 Wiley Periodicals LLC.)

Competing Interests: We declare no competing interests. This work was supported by the US Agency for International Development through the MOMENTUM Safe Surgery in Family Planning and Obstetrics award (cooperative agreement number 7200AA20CA00011). The contents of this article do not necessarily reflect the views of the US Agency for International Development or the US Government.

Introduction: Disturbed paternal epigenetic status of imprinted genes has been observed in infertility and recurrent spontaneous abortions. Shallow placentation has been associated with early-onset preeclampsia. Hence, the present study aimed to investigate the methylation patterns of imprinted genes involved in placental development, in the spermatozoa of partners of women experiencing preeclampsia., Methods: The study involved recruitment of couples into preeclampsia (n = 14) and control (n = 25) groups. Methylation analysis of imprinted gene differentially methylated regions (DMRs) and LINE1 repetitive element was carried out by pyrosequencing in the spermatozoa and placental villi. Global 5 mC levels in the spermatozoa were measured through ELISA. Expression of imprinted genes was quantified in the placental villi by real time qPCR. Association of birth weight with DNA methylation and gene expression was assessed., Results: KvDMR, PEG3 DMR, PEG10 DMR and DLK1-GTL2 IG-DMR were differentially methylated in the spermatozoa and placental villi of preeclampsia group. Global 5 mC content and LINE1 methylation levels did not differ between the spermatozoa of the two groups. Increased transcript levels of PEG3, IGF2, DLK1, PHLDA2 and CDKN1C were observed in the preeclamptic placental villi. Birth weight showed significant association with KvDMR, PEG10 DMR, DLK1-GTL2 IG-DMR and LINE1 methylation levels in the spermatozoa. DLK1 expression levels showed a negative association with birth weight., Discussion: The study highlighted the paternal contribution to early-onset preeclampsia, in the form of disrupted sperm DNA methylation patterns at imprinted gene loci. These loci, after further evaluation in future studies, could serve as sperm-based preeclampsia predictive markers, for couples planning pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Preeclampsia (PE) is a pregnancy complication marked by high blood pressure, posing risk to maternal and fetal health. "Genomic imprinting", an epigenetic phenomenon regulated by DNA methylation at Differently Methylated Regions (DMR's), influences placental development. Research on circulating extracellular vesicles (EVs) in PE suggests them as potential source for early biomarkers, but methylation status of EV-DNA in Preeclampsia is not reported yet., Methods: This study examines the methylation and expression profile of imprinted genes - PEG10, PEG3, MEST, and DLK1 in circulating EVs of 1 st and 3 rd trimester control and early onset preeclampsia (EOPE) pregnant women (n = 15) using pyrosequencing and qRT-PCR respectively., Results: In 1 st trimester, PEG3 was significantly hypermethylated, whereas no significant methylation changes were noted in PEG10 and MEST in EOPE. In 3 rd trimester, significant hypomethylation in PEG10, PEG3 and IGDMR was observed whereas significant hypermethyaltion noted in MEST. mRNA expression of PEG10, PEG3 and DLK1 was not affected in circulating EVs of 1 st trimester EOPE. However, in 3 rd trimester significant increased expression in PEG10, PEG3 and DLK1 noted. MEST expression was reduced in 3 rd trimester EOPE. No correlation was observed between average DNA methylation and gene expression in PEG10 and PEG3 in 1 st trimester. However, in 3 rd trimester, significant negative correlation was noted in PEG10 (r = -0.426, p = 0.04), PEG3 (r = -0.496, p = 0.01), MEST (r = -0.398, p = 0.03) and DLK1 (r = -0.403, p = 0.03)., Discussion: The results of our study strengthen the potential of circulating EVs from maternal serum as non-invasive indicators of placental pathophysiology, including preeclampsia., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bacterial infections are a common cause of sepsis, often leading to high patient mortality. Such infections are challenging to treat due to bacterial resistance to many existing drugs. Erythromycin (Ery) is a macrolide antibiotic used against bacterial infections with reported resistance. Recently, synthetic poly-lactide co-glycolic acid (PLGA) polymer nanoparticles (NPs) have displayed improved drug delivery characteristics and biocompatibility. In this study, PLGA-Ery NPs were synthesized by the o/w emulsion diffusion method, having a particle size of 159 ± 23 nm and displayed 71.89 % of encapsulation efficiency. The PLGA-Ery NPs showed 1.5, 2.1 and 1.5-fold improved MIC and antibacterial efficacy against E. coli, S. aureus, and P. aeruginosa, respectively than the pure drug. As illustrated by scanning electron microscopy, PLGA-Ery NPs caused damage to the bacterial cell walls. Furthermore, a surface coating with PLGA-Ery NPs on a glass surface showed efficient inhibition (>90 %) of the biofilm formation by P. aeruginosa, as determined by fluorescence microscopy and MTT assay. This study demonstrates that PLGA-Ery NPs can increase the efficiency of erythromycin and can suppress the growth and biofilm formation of P. aeruginosa. Such polymeric nanoparticles drug nanoformulations have potential as an antimicrobial and as a surface coating for medical devices., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Vandana Ghormade reports financial support was provided by Indian Council of Medical Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To observe the variability in the plasma concentrations and pharmacokinetic-pharmacodynamic (PK-PD) profiles of first-line antitubercular drugs in pulmonary tuberculosis (TB) patients with and without diabetes mellitus (DM)., Methods: Newly diagnosed pulmonary TB patients aged 18-60 years with or without DM were included in the study. Group I (n = 20) included patients with TB, whereas group II (n = 20) included patients with both TB and DM. After 2 weeks of therapy, plasma concentrations and other PK-PD parameters were determined. Improvements in clinical features, X-ray findings, sputum conversion, and adverse drug reactions (ADRs) were assessed after 2 months of therapy., Results: Isoniazid displayed non-significantly higher plasma concentrations in diabetic patients, along with a significantly (P < 0.05) longer elimination half-life (t 1/2 ). Rifampicin plasma concentrations at 4, 8, and 12 h were significantly (P < 0.05) lower, and it displayed significantly (P < 0.05) lower area under the curve (AUC 0-12 and AUC 0-∞ ), shorter t 1/2 , higher clearance (Cl), and a lower AUC 0-∞ /MIC ratio in diabetic patients. Pyrazinamide and ethambutol showed non-significantly higher plasma concentrations, AUC 0-12 , AUC 0-∞ , and t 1/2 in diabetic patients. The improvements in clinical features, X-ray findings, sputum conversion, and ADRs were comparable in both groups., Conclusions: The presence of DM in TB patients affects the PK-PD parameters of isoniazid, rifampicin, pyrazinamide, and ethambutol variably in the Indian population. Studies with a larger number of patients are required to further elucidate the role of DM on the PK-PD profile of first-line antitubercular drugs and treatment outcomes in TB patients with concomitant DM., Trial Registration: CTRI/2021/08/035578 dated 11/08/2021., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Contracture and thickening of the coracohumeral ligament (CHL) occur in patients with adhesive capsulitis. This adversely affects the movement and function of the shoulder joint. There is limited evidence that explores the effectiveness of an isolated steroid injection into the CHL in combination with physical therapy. This prospective randomized control trial aimed to evaluate the clinical effects of ultrasonography-guided corticosteroid injection compared to a sham injection into the CHL in subjects with adhesive capsulitis., Methods: Forty patients (23 males, 52.2 ± 8 years of age) with unilateral adhesive capsulitis (with 5.4 ± 2 months' mean duration of symptoms) were randomly assigned to either the experimental or control group. Both groups received ultrasonography-guided injections into the CHL. The experimental group (n = 20) received corticosteroids and the control group (n = 20) received a sham lidocaine injection. All subjects underwent supervised conventional physical therapy 3 times a week for 3 months. Subjects were evaluated for improvements in pain, range of motion, and disability at 6 and 12 weeks compared with preinjection baseline measurements. Data were compared statistically across groups and times at P < .05. The CHL thickness was compared at baseline across sides using paired t tests., Results: The experimental group showed statistically greater improvements in pain, functional scores, flexion, abduction, and internal and external rotation range of motion at 12 weeks compared with the control group. Pain reduction was observed in both groups at 6 and 12 weeks, but the experimental group exhibited significantly greater reductions. The CHL was significantly thicker on the affected side than on the unaffected side (P < .001)., Discussion and Conclusion: This study partially supported the hypothesis. Notably, significant improvements in pain, range of motion, and functional scores were observed at 12 weeks in the experimental group. The greater improvements in pain and external rotation may have resulted in lower disability scores in the experimental group. The results emphasize the importance of targeted intervention into the CHL., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Chemical fortification and dose supplementation of vitamin B 12 are widely implemented to combat deficiency symptoms. However, in situ, fortification of vitamin B 12 in food matrixes can be a promising alternative to chemical fortification. The present study aimed to produce vitamin B 12 -rich, probiotic guava juice fermented with Levilactobacillus brevis strain KU15152. Pasteurized fresh guava juice was inoculated with 7.2 log CFU mL -1 L. brevis strain KU15152 and incubated for 72 h at 37 °C anaerobically. The antioxidants, total phenolic compounds, vitamin B 12 production, sugars, organic acids, pH and viable count were analyzed at 24, 48 and 72 h of incubation. The fermented juice was stored at 4 °C, and the changes in its functional properties were analyzed at 7-day intervals up to 28 days of storage., Results: During fermentation, the bacteria cell count was increased from 7.01 ± 0.06 to 9.76 ± 0.42 log CFU mL -1 after 72 h of fermentation and was decreased to 6.94 ± 0.34 CFU mL -1 during storage at 4 °C after 28 days. The pH, total soluble solids, crude fiber, citric acid and total sugars decreased, while titratable acidity, total protein, antioxidants, phenolic compounds and lactic acid contents increased during fermentation. The fermented guava juice exhibited higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS)) radical scavenging activities (85.97% and 75.97%, respectively) at 48 h of fermentation. The concentration of active vitamin B 12 in the sample reached 109.5 μg L -1 at 72 h of fermentation. However, this concentration gradually decreased to 70.2 μg L -1 during the storage period. During storage for 28 days at 4 °C, both the fermented and control guava juices exhibited a decline in antioxidant and phenolic compound concentrations. Furthermore, the addition of 20% honey and guava flavor enhanced the organoleptic properties and acceptability of fermented guava juice., Conclusion: The value-added fermented guava juice could be a novel functional food product to combat vitamin B 12 deficiency. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Purpose: The aim of this study was to determine the effects of 2% pilocarpine ophthalmic solution on the depth of field and the pupil size of human eye in the presbyopic population., Settings and Design: Prospective experimental study., Methods: The prospective study included 120 presbyopic people aged between 40 and 55. All willing subjects underwent a comprehensive eye examination that included measuring the visual acuity for distance and near, retinoscopy, refraction, anterior and posterior segment examination, depth of field, and pupil size in room illumination. Following a preliminary examination, 2% pilocarpine ophthalmic solution was instilled in both eyes, and after various intervals of 15, 30, and 45 min, the depth of field and the pupil size were measured., Results: Before instillation of 2% pilocarpine solution, the mean pupil size was 0.34 mm with a standard deviation (SD) of ±0.37. After instillation, the mean pupil size changed to 2.20, 1.91, and 1.57 mm with SD of ±0.43, ±0.27, and ±0.34 mm, respectively, in 15, 30, and 45 min time intervals. Initial mean depth of field also changed from 1.76 D (SD ± 0.20) to 1.72, 1.65, and 1.59 D with SD of ±0.20, ±0.16, and ±0.22 D, respectively, in 15, 30, and 45 min time intervals., Conclusion: The study concludes that pupillary miotics create a pinhole effect after the instillation of 2% pilocarpine ophthalmic drop, extending the depth of field. The effect was highly clinically significant at 45 min with a P value <0.001., (Copyright © 2024 Indian Journal of Ophthalmology.)

With ∼50% recurrent pregnancy loss cases being termed idiopathic (iRPL), understanding of contribution of male factors to iRPL is still lacking. Higher prevalence of sperm DNA fragmentation index (DFI) and lower sperm 5-methylcytosine (5-mC) levels have been previously reported in male partners of iRPL couples and shed light on importance of the male gamete in maintenance of a successful pregnancy. The present study aimed to determine the serum sex steroid hormone levels, sperm DFI and 5-mC and correlation between them in male partners of fertile and iRPL couples. Further, correlation between sperm DFI and 5-mC with semen parameters and paternal age in both groups were determined. 36 male partners of fertile couples and 45 male partners of women experiencing iRPL were enrolled for this study and semen and blood samples were collected. Serum testosterone and estradiol levels were measured by ELISA; sperm DFI and global 5-mC were determined by TUNEL assay and ELISA respectively. Significantly higher serum testosterone levels were noted in the iRPL group ( p  = 0.028). Incidence of sperm DNA fragmentation was found to be higher in the iRPL study group but with no significance difference. No significant differences in sperm 5-mC values were noted. Upon correlation analysis within both groups, strong significant negative correlation of sperm DFI % and 5-mC % was observed in the control group ( p  < 0.001) but not the iRPL group ( p  = 0.249). Hence, we infer that with lower 5-mC levels in sperm genome, there is a higher incidence of sperm DFI in fertile men. However, this trend is not noted in men of iRPL group which could possibly be due to other underlying epigenetic alterations in genomic regions probably unsusceptible to fragmentation. On the other hand, no significant correlations of semen parameters, testosterone, estradiol and paternal age with sperm DFI and 5-mC were noted in both groups.

Objectives: To study the impact of carbohydrate counting vs. fixed-meal plan on glycemic control, quality of life (QoL) and diabetes-related emotional distress in children with Type 1 diabetes mellitus (T1DM)., Methods: Children aged 6-18 y with T1DM of duration >1 y were eligible for the study if they were on multiple daily injections of insulin and regularly monitoring blood glucose. Those with celiac disease, hypothyroidism, any underlying chronic renal/liver/systemic disease or HbA1c >13% were excluded. Both groups received education on diabetes management and healthy diet. In the intervention arm, parents were taught to quantify carbohydrate content and modify insulin doses according to insulin-carbohydrate ratio. The control arm had dietary prescription according to recommended dietary allowance and food exchange list. Standard validated questionnaires were used to assess the QoL and emotional distress related to diabetes., Results: One hundred twenty five patients (61 intervention, 64 controls) were enrolled and 91.8% and 84.3%, respectively, completed 6-mo follow-up. There was a reduction in HbA1c in both the groups, but was not statistically significant within or between groups {Intervention: 8.9 (1.4) to 8.6 (1.5) vs. control: 9.1 (1.6) to 8.8 (1.9), [95% CI 8.3-9.3 vs. 8.3-9.0, intention to treat (ITT), p = 0.63]}. There was a significant reduction in diabetes distress in the intervention group; DAWN Problem Areas in Diabetes Questionnaire (PAID) score with a median (interquartile range) of 21 (11-33) vs. control: 27 (20-40), (p = 0.04)., Conclusions: Patients in the carbohydrate-counting group demonstrated lower diabetes distress scores and less emotional burnout compared to fixed-meal plan over a 6 mo period though overall glycemic control was comparable between groups., Competing Interests: Declarations Conflict of Interest None., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Purpose: Phosphate binders (PB) are integral to hyperphosphatemia management in patients with end-stage kidney disease. PB efficacy is adversely affected by nonadherence and limited phosphate-binding capacity relative to dietary intake. Oxylanthanum carbonate is an investigational novel nanotechnology product that combines lanthanum, which has the highest binding capacity of available PBs, with a smaller pill size that is swallowed with water rather than chewed. This study's objective was to demonstrate the pharmacodynamic equivalence of orally administered oxylanthanum carbonate to lanthanum carbonate (LC) in healthy subjects., Methods: In this phase one, single-center, randomized, open-label study, healthy subjects were treated with oxylanthanum carbonate swallowable tablets 1000 mg three times/day and LC chewable tablets 1000 mg three times/day in a two-way crossover design. The primary pharmacodynamic variable was the least squares mean (LSM) change in urinary phosphate excretion from baseline to the evaluation period (Days 1-4 of treatment)., Findings: A total of 80 subjects were randomized and 75 received all doses. The LSM change in urinary phosphate excretion from Baseline to the Evaluation (Treatment) Period was similar for both oxylanthanum carbonate (-320.4 mg/day [90% CI: -349.7, -291.0]) and LC (-324.0 mg/day [90% CI: -353.3, -294.7]); the between-group LSM difference was 3.6 [90% CI: -37.8, 45.1] mg/day. Both drugs were well tolerated with an equal incidence of adverse events., Implications: Thus, oxylanthanum carbonate was bioequivalent to LC in healthy subjects and well tolerated. Oral oxylanthanum carbonate may provide an option for patients with chronic kidney disease and hyperphosphatemia for whom chewing tablets is disliked, inconvenient, or difficult., Clinical Trial Registration Number: NCT06218290., Competing Interests: Declaration of competing interest Steve Hasal, Guru Reddy, and Shalabh Gupta are employees of Unicycive Therapeutics, Inc. Vandana Mathur and Michael Walker are consultants for Unicycive Therapeutics, Inc. Editorial support was funded by Unicycive Therapeutics, Inc., (Copyright © 2024 Unicycive Therapeutics, Inc. Published by Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) is a complex debilitating condition leading to permanent life-long neurological deficits. Estrogen (E2) treatment is known to be neuroprotectant in SCI. This hormone is highly pleiotropic and has been shown to decrease apoptosis, modulate calcium signaling, regulate growth factor expression, act as an anti-inflammatory, and drive angiogenesis. These beneficial effects were found in our earlier study at the low dose of 10 µg/kg E2 in rats. However, the dose remains non-physiologic, which poses a safety hurdle for clinical use. Thus, we recently devised/constructed a fast release nanoparticle (NP) estrogen embedded (FNP-E2) construct and tested a focal delivery system in a contused SCI rat model which showed protection in the short run. In the current study, we have developed a novel slow-release NP estrogen (SNP-E2) delivery system that shows sustained release of E2 in the injured spinal cord and no systemic exposure in the host. The study of E2 release and kinetics of this SNP-E2 construct in vitro and in vivo supported this claim. Delivery of E2 to the injured spinal cord via this approach reduced inflammation and gliosis, and induced microglial differentiation of M1 to M2 in rats after SCI. Analysis of spinal cord samples showed improved myelination and survival signals (AKT) as demonstrated by western blot analysis. SNP-E2 treatment also induced astrocytic differentiation into neuron-like (MAP2/NeuN) cells, supported the survival of oligodendrocyte precursor cells (OPC), and improved bladder and locomotor function in rats following SCI. These data suggest that this novel delivery strategy of SNP-E2 to the injured spinal cord may provide a safe and effective therapeutic approach to treat individuals suffering from SCI., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Chronic obstructive pulmonary diseases (COPD) is characterized by airflow limitation, chronic inflammation and airway remodeling (AR) in airways and lung parenchyma. AR, a lung response, involves mucus production, airflow issues, and structural changes. It is exacerbated by neurogenic inflammation from activated sensory nerves, highlighting the interplay between neuronal and immune regulation in COPD. Sirtuins play a crucial role in lung remodeling, with SIRT-2 being the least studied. Present study explores how SIRT-2 regulates neurogenic inflammation and fibrosis in experimental BALB/c mice with cigarette smoke-induced COPD. Mice from each group, except the control, were exposed to CS for 60 days and AK-7 (100ug/kg and 200ug/kg) was administered intranasally. The study evaluated lung injury and inflammation marked by increased Cortisol, ACTH, COX-2 and LDH in COPD group with its attenuation by SIRT-2 inhibition. Additionally, CS exposure exhibited neurogenic inflammation represented by activated TPRV1 and TRPM8, elevated neuromediators levels (dopamine, acetylcholine, substance P, serotonin) and their respective receptors which were mitigated by AK-7. CS exposure enhanced fibrosis by targeting the fibrotic cascade, enhancing MMP-9, total collagen, hydroxyproline, and upregulating αSMA, MUC5AC, TGF-β, PKA, GATA-3, FOXO3, and STAT-6. SIRT-2 inhibition effectively reversed all these factors suppressing fibrosis further supported by downregulated SIRT-2 expression and histopathological studies where collagen deposition and mucus production were also attenuated by AK-7. Molecular docking revealed strong binding affinity of certain protein such as COX-2, D5DR and 5HT with AK-7. Overall, targeting SIRT-2 to modulate neuro-immune interplay presents a promising therapeutic approach for addressing AR in COPD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Surveillance of drug resistance and the discovery of novel targets-key objectives in the fight against malaria-rely on identifying resistance-conferring mutations in Plasmodium parasites. Current approaches, while successful, require laborious experimentation or large sample sizes. To elucidate shared determinants of antimalarial resistance that can empower in silico inference, we examined the genomes of 724 Plasmodium falciparum clones, each selected in vitro for resistance to one of 118 compounds. We identified 1448 variants in 128 recurrently mutated genes, including drivers of antimalarial multidrug resistance. In contrast to naturally occurring variants, those selected in vitro are more likely to be missense or frameshift, involve bulky substitutions, and occur in conserved, ordered protein domains. Collectively, our dataset reveals mutation features that predict drug resistance in eukaryotic pathogens.

Loss-of-function ABCC8 variants are the commonest cause of congenital hyperinsulinism. On a systematic search of our databases, the p.(Gly111Arg) ABCC8 variant was identified in 26 individuals, of which 23 were from the Indian Agarwal community. Haplotype analysis subsequently confirmed that p.(Gly111Arg) is a founder variant in the Agarwal population., (© 2024 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd.)

Supramolecular assemblies based on the twisted donor-acceptor-donor (D-A-D) building block Qx-Ind have been developed, which interestingly, due to the balanced angle of twist (38.28°), high intermolecular charge transfer, and crystallization induced emission (CIE) characteristics, exhibit high molar absorptivity and a long-lived "lighted" excited state at the supramolecular level. The validity of the design concept was examined by preparing CIE active D-A-D system Qx-Indaz (weak donor, low angle of twist: 35.45°), in which, due to the insertion of an additional binding site for noncovalent interactions, a drastic change in the photophysical behavior is observed. The combined spectroscopic studies of all the compounds unveil the strong impact of modulation of the angle of twist and intermolecular charge transfer upon photophysical behavior in the aggregated state. Due to the favorable photophysical behavior, the supramolecular assemblies of Qx-Ind exhibit high type I photosensitizing activity in comparison to Qx-Indaz . The superior type I photosensitizing activity of Qx-Ind assemblies is manifested in their ability to efficiently catalyze the aerobic oxidative synthesis of quinazolin-4(3 H )-ones (via type I ROS) from 2-aminobenzamide and aromatic aldehydes in the absence of additional additives (base/oxidant). Unlike photocatalytic nanoassemblies reported in the literature, due to the CIE characteristics, Qx-Ind does not require preliminary preparation and could be directly introduced in the solid state to reaction media. Thus, the present work demonstrates a simple strategy of upgrading type I photosensitizing activity by improving the ground/excited state behavior of a twisted D-A-D system through modulation of the angle of twist and charge transfer characteristics.

The identification of novel drug targets for the purpose of designing small molecule inhibitors is key component to modern drug discovery. In malaria parasites, discoveries of antimalarial targets have primarily occurred retroactively by investigating the mode of action of compounds found through phenotypic screens. Although this method has yielded many promising candidates, it is time- and resource-consuming and misses targets not captured by existing antimalarial compound libraries and phenotypic assay conditions. Leveraging recent advances in protein structure prediction and data mining, we systematically assessed the Plasmodium falciparum genome for proteins amenable to target-based drug discovery, identifying 867 candidate targets with evidence of small molecule binding and blood stage essentiality. Of these, 540 proteins showed strong essentiality evidence and lack inhibitors that have progressed to clinical trials. Expert review and rubric-based scoring of this subset based on additional criteria such as selectivity, structural information, and assay developability yielded 67 high priority candidates. This study also provides a genome-wide data resource and implements a generalizable framework for systematically evaluating and prioritizing novel pathogenic disease targets.

Purpose: Sarcopenic obesity, characterized by increased adiposity with low skeletal muscle mass, contributes to frailty and the development of chronic disease. Data on sarcopenic obesity in survivors of childhood acute lymphoblastic leukemia (cALL) is limited., Methodology: A cross-sectional study on 65 cALL survivors (7-18 years, > 2 years from treatment completion) was conducted on cALL survivors with the primary outcome to determine the prevalence of sarcopenic obesity. Sarcopenic obesity was defined as patients with a positive Fat Mass Index (FMI) z-score with a negative Skeletal Muscle Index (SMI) z-score, measured using a Dual-Energy Xray Absorptiometry (DXA) scan. In addition, we assessed the factors associated with sarcopenic obesity by multivariable regression analysis., Results: The mean (± SD) age was 12.9 (± 3.2) years, the median (Interquartile Range) time since diagnosis was 6.5 (5.9;8) years, and 66% received cranial radiotherapy. Central obesity, insulin resistance, and metabolic syndrome were seen in 21.5%, 23.1%, and 21% respectively. DXA-derived body composition variables revealed higher fat percentage despite normal body mass index (BMI) and lower muscle mass compared to the general population. Sarcopenic obesity was seen in 21 (34%) of survivors. On multivariable regression analysis, age at diagnosis (OR: 0.95 (95% CI: 0.92-0.98), p = 0.02), central obesity (OR: 18.99 (95% 2.32-155.5), p = 0.006) and insulin resistance (OR: 10.2 (95% CI: 1.75-59.09), p = 0.01) were associated with sarcopenic obesity., Conclusions: Sarcopenic obesity, an early clinical indicator for metabolic disease despite normal BMI, was significantly worse in children diagnosed with ALL at a younger age and was associated with central obesity and insulin resistance, which may contribute to adverse outcomes later in life., Competing Interests: Declarations. Ethics: Ethics approval was taken by the AIIMS-New Delhi Ethics Committee for Post-Graduate Research vide Ref-no: IECPG-628/28.11.2019, RT-08/19.12.2019, and the research was conducted per the ethical guidelines laid down by the Helsinki Declaration. Consent to participate: Written informed consent was obtained from the parents and children provided assent (verbal and written) wherever necessary. Consent to publish: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Telemedicine has revolutionized health care by significantly enhancing accessibility and convenience, yet barriers remain, such as providers' challenges with technology use. With advancements in telemedicine technologies, understanding the viewpoints of patients and providers is crucial for an effective and acceptable telemedicine service. This study reports the findings on the usability and effectiveness of the HelixVM artificial intelligence powered platform, analyzing key aspetcs like asynchronous health care, access, time efficiency, productivity, data exchange, security, privacy, and quality of care from patient and provider perspectives., Objective: This study aims to assess the usability and effectiveness of the HelixVM marketplace platform., Methods: We recruited 102 patients and 12 providers in a mixed methods study design involving surveys and in-depth structured interviews with a subset of the providers. The survey questionnaires are a modified version of the Telehealth Usability Questionnaire. We analyzed patient data using descriptive statistics and exploratory factor analysis to identify latent demographic patterns. For provider data, we used a deductive thematic analysis approach to identify key themes from the interviews and interpreted overall sentiments of the providers as negative, neutral, or positive. We also calculated percentages of different provider responses from the survey and interviews, where applicable., Results: Overall, 86.3% (88/102) of the patients reported satisfaction with HelixVM, and 89.2% (91/102) indicated that they would use the services again. A total of 91.1% (93/102) of the patients agreed that HelixVM improves access to health care and is an acceptable way to receive health care, and 98% (100/102) agreed it saves time. Chi-square tests demonstrated statistical significance for all survey questions (P<.001). The results from factor analysis show a higher propensity of middle-aged women, who had a fast-track encounter type, who self-reported a medium level of technology savviness, and who are residing in the South region of the United States rating the platform more positively. With regard to the providers, the thematic analysis identified themes of asynchronous medicine in terms of the accessibility and quality of care, time and productivity, integration within the workflow, data exchange, and artificial intelligence triage. Certain challenges regarding incomplete data in patient charts and its impact on provider time were cited. Suggestions for improvements included options to ensure the completeness of patient charts and better screening to ensure that only asynchronous, qualified patients are able to reach the provider., Conclusions: Overall, our study findings indicate a positive experience for patients and providers. The use of fast-track prescription was considered favorable compared to traditional telemedicine. Some concerns on data completeness, gaps, and accuracy exist. Suggestions are provided for improvement. This study adds to the knowledge base of existing literature and provides a detailed analysis of the real-world implementation of a telemedicine market-place platform., (©Ekta Jain, Srishti Gupta, Vandana Yadav, Stan Kachnowski. Originally published in JMIR Formative Research (https://formative.jmir.org), 25.11.2024.)

Recurrent spontaneous abortions (RSA) is defined as a loss of two or more consecutive clinically recognized pregnancies before the 20th week of gestation. In RSA, several causative maternal factors are known, but still, 50% of the cases remain unexplained. Evidence suggests that paternal factors are also equally important. Epigenetic phenomenon such as genomic imprinting and regulation of gene expression by miRNAs plays an important role in embryonic and placental development. Two large miRNA clusters, C14MC (Chromosome 14 microRNA cluster) and C19MC (Chromosome 19 microRNA cluster) are imprinted and expressed in the placenta during pregnancy and are known to regulate functionally important processes such as the trophoblast proliferation, adhesion, and migration. Hence, we studied the DNA methylation at the Differentially Methylated Regions (DMRs) of these clusters in spermatozoa and chorionic villi by pyrosequencing. In Spermatozoa, few Cytosine followed by Guanosine (CpG) sites at DMRs of C14MC and C19MC showed significant hypermethylation. In Chorionic villi, CpG sites showed significant hypomethylation in the RSA group as compared to control group. Semen parameters like sperm concentration, sperm motility, morphology, and chromatin compaction were comparable in control and RSA groups. The study suggests aberrant DNA methylation in spermatozoa and chorionic villi at DMRs of both miRNA coding clusters to be associated with RSA., Competing Interests: Declarations. Ethical Approval: The study was approved by the Institutional Ethics Committee for Clinical Studies (National Institute for Research in Reproductive and Child Health); 332/2018. Conflict Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Arylomycin, a potent antibiotic targeting bacterial signal peptidase, is difficult to synthesize experimentally due to its poor to moderate yields and the formation of a mixture of compounds. A recent experimental bioengineering work shows that the core of arylomycin can be efficiently synthesized by engineering the cytochrome P450 enzyme from Streptomyces sp.; however, the mechanism of the same was not elucidated. Herein, we have thoroughly investigated the mechanism behind the evolution of the enzyme for the synthesis of the arylomycin core via C-C bond formation in the CYP450 enzyme using hybrid QM/MM calculations, MD simulations, and DFT calculations. We show that strategic mutations such as (a) G-101 → A facilitate biaryl coupling by subtly pushing the substrate and (b) the Q-306 → H mutation creates a strong pi-pi interaction with the substrate that brings the two phenol rings of the substrate closer to undergo C-C coupling. Importantly, our QM/MM calculations show that for efficient C-C formation, the reaction should proceed via the biradical mechanism rather than hydroxylation.

Background/objectives: Self-care has great potential to benefit consumers and health systems, but its mainstream adoption is hindered by a systemic lack of consumer health literacy (HL). Published data on consumer awareness of self-care and HL are limited for regions in Asia, and are needed to develop interventions to enhance HL and self-care for diverse populations in this region. The aim of this research was to describe and analyze patterns of HL and awareness of self-care among consumers in Asia., Methods: We conducted a mixed-methods study comprising qualitative focus group discussions (FGDs; 64 participants) followed by a quantitative online survey (1200 participants) among consumers in four Asian countries (India, Philippines, Malaysia, and Republic of Korea). We examined five dimensions of HL and self-care relevant to consumers: actively managing health; confidence/skills to find and access health information; confidence/skills to appraise information; support from social circle; and support from healthcare providers. From the quantitative survey, responses for 16 questions covering the five dimensions were used to calculate the Consumer Health Literacy Quotient (CHLQ; normalized range 0-100), an index we developed to assess HL in the context of personal wellness and self-treatable conditions. Latent class analysis (LCA) was applied to identify distinctive patterns of consumer HL within the sample., Results: The mean CHLQ was 75 out of 100 (SD ± 12.9), indicating 'moderate' levels of consumer HL across the countries. LCA identified five distinct consumer HL profiles, differing in their average CHLQ (overall score) and along the CHLQ dimensions. Consistent with CHLQ results, the profiles differed in their response patterns for common self-manageable ailments., Conclusions: This study identified distinct patterns of HL and awareness of self-care among consumers in four Asian countries through combined use of the CHLQ and quantitative profiling. This offers a promising approach for understanding self-care-related HL among consumers in Asia. Our findings on patterns of strengths and weakness in specific dimensions of HL and self-care in diverse populations can inform research, communications, and targeted interventions to empower consumers and foster self-care.

The heterotrimeric protein phosphatase 2A (PP2A) complex catalyzes about half of Ser/Thr dephosphorylations in eukaryotic cells. A CAG repeat expansion in the neuron-specific protein PP2A regulatory subunit PPP2R2B gene causes spinocerebellar ataxia type 12 (SCA12). We established five monoallelic missense variants in PPP2R2B (four confirmed as de novo) as a cause of intellectual disability with developmental delay (R149P, T246K, N310K, E37K, I427T). In addition to moderate to severe intellectual disability and developmental delay, affected individuals presented with seizures, microcephaly, aggression, hypotonia, as well as broad-based or stiff gait. We used biochemical and cellular assays, including a novel luciferase complementation assay to interrogate PP2A holoenzyme assembly and activity, as well as deregulated mitochondrial dynamics as possible pathogenic mechanisms. Cell-based assays documented impaired ability of PPP2R2B missense variants to incorporate into the PP2A holoenzyme, localize to mitochondria, induce fission of neuronal mitochondria, and dephosphorylate the mitochondrial fission enzyme dynamin-related protein 1. AlphaMissense-based pathogenicity prediction suggested that an additional seven unreported missense variants may be pathogenic. In conclusion, our studies identify loss-of-function at the PPP2R2B locus as the basis for syndromic intellectual disability with developmental delay. They also extend PPP2R2B-related pathologies from neurodegenerative (SCA12) to neurodevelopmental disorders and suggests that altered mitochondrial dynamics may contribute to mechanisms., (© The Author(s) 2024. Published by Oxford University Press.)

Sepsis-induced Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) pose life-threatening risks due to an excessive activation of proinflammatory cytokines via the JAK pathway. Currently, no confirmed drug treatment exists for ALI. In this study, we explored JAK1 as a potential therapeutic target to address this issue. This study evaluates lapachol, a bioactive secondary metabolite, for its potential in treating sepsis-induced Acute Lung Injury (ALI). Lapachol was selected based on in-silico analyses such as binding energy, RMSD, RMSF, H-bond graphs, and lig plots supported the hypothesis that Lapachol binds to JAK1 in a manner similar to Tofacitinib JAK1/3 inhibitor (Positive control). Lapachol, derived from the heartwood of Tecomella undulata, was used in this investigation. Swiss albino mice were categorized into control, LPS treated, positive control (Tofacitinib), and experimental groups (Lapachol at 20 and 40 mg/kg doses). Throughout the experiment, mice behaviour was monitored, and euthanasia was performed at 12 and 24-h intervals. Various analyses, including body weight, W/D ratio, lung weight/body weight ratio, flow cytometry of BAL fluid (at 12 and 24 h), histology, myeloperoxidase assays were performed. Results indicated that both Tofacitinib and Lapachol significantly reduced ALI markers, including lung weight/body weight ratio, cell counts, and granulocytes in bronchoalveolar lavage fluid. Moreover, histopathology and MPO analysis suggested that Lapachol, particularly at 40 mg/kg, exhibited anti-inflammatory effects comparable to Tofacitinib. Conclusively, the findings suggest that Lapachol possesses the potential to inhibit JAK1 kinase domains and mitigate ALI associated with sepsis similar to Tofacitinib., Competing Interests: Declaration of competing interest The authors declares no other conflicts of interest related to this research., (Copyright © 2024. Published by Elsevier B.V.)

Background: The unfolded protein response (UPR) pathway serves as a crucial mechanism enabling plants to perceive, respond to, and shield themselves from adverse environmental conditions. Inositol-requiring enzyme 1 (IRE1) is one of the key players of the UPR, and resides in the endoplasmic reticulum (ER) within the cell. This study provides a comprehensive analysis of 195 IRE1 genes across 90 diverse plant species, with a focus on their identification and characterization., Results: To decipher the functions of IRE1 family members, we investigated the evolution and spread of IREs in plants and analysed their structural and localization characteristics. Our detailed cis-element analysis revealed unique IRE1 regulation patterns in different plant species. Furthermore, gene expression analysis revealed tissue-specific and heat stress-responsive expression patterns of TaIRE1s, which were subsequently confirmed via quantitative gene expression analysis. TaIRE1-6A was upregulated in response to dithiothreitol (DTT) treatment as well as heat stress. This finding suggests that IRE1 might play a role in linking the UPR pathway and the heat stress response (HSR)., Conclusions: Our findings provide a comprehensive understanding of the evolution and expansion of IRE1 genes in different plant species. These findings provide a foundation for further in-depth research on the functional diversity of IREs in nutritious crops following polyploidization. By linking the UPR with HSR, IRE1 could be a key contributor to wheat's resilience against heat stress. Additionally, this connection offers important insights for future functional studies in other crops. Thus, this knowledge could be used for engineering climate resilience in crops such as wheat., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

A new series of acyl hydrazones have been synthesized from 4-chloro-8-nitro-1,2-dihydroquinoline-3-carbaldehyde. These compounds were characterized using various spectroscopic techniques. Density functional theoretical (DFT) studies were conducted to understand the correlation between electronic parameters and biological activity. The biological activity of the compounds was theoretically examined through molecular docking and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis. The compounds demonstrated high absorption rates and were found to be non-hepatotoxic. Preliminary cytotoxicity screenings against HeLa cell lines identified compound 7 as the most potent, with an IC 50 value of 18.8 μM. This compound was further selected for bioimaging studies. The results indicate that compound 7 induces apoptosis at its IC 50 concentration, suggesting its potential as an anticancer agent., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Photosensitizing assemblies based on twisted intramolecular charge transfer (TICT) active donor-acceptor-donor (D-A-D) system BrTPA-Qx having bromine atoms at the periphery have been developed. Through strategic incorporation of bromine atoms at the para -position to the nitrogen-carbon bonds of phenyl rings at the periphery, halogen-halogen interactions are induced in BrTPA-Qx nanoassemblies in H 2 O:DMSO (99:1) solution. Hence, the anti-heavy atom effect is induced, and the limitations of TICT (dark excited state) and heavy atom effect (triplet deactivation via radiative decay) could be overcome. Because of TICT and anti-heavy atom effect, supramolecular BrTPA-Qx nanoassemblies demonstrate high efficiency in promoting activation of aerial oxygen via electron and energy transfer pathways in aqueous media. The significant influence of the stabilized TICT state and anti-heavy-atom effect in controlling the ROS generation was validated through in-depth solvent-dependent photophysical studies and investigations of the structure-activity relationship in several model compounds. The notable photosensitizing activity of BrTPA-Qx nanoassemblies is manifested in their ability to efficiently catalyze the oxidative coupling of benzylamine (via type I and type II mechanisms), Knoevenagel condensation of aromatic aldehydes (type II), and oxidative hydroxylation of arylboronic acids (type I) under mild conditions.

The building block Pyra-Chol has been designed and synthesized, which exhibits different achiral morphologies in good solvents, forming nanospheres in THF and nanoflowers in 1,4-dioxane. In the presence of water as a poor cosolvent, Pyra-Chol demonstrates an agnostic behavior, generating left-handed superhelices in the water:THF (80:20) solvent system. However, when the good solvent is switched to 1,4-dioxane, a change in chirality is observed in the water:1,4-dioxane (30:70) solvent system, resulting in the formation of fused nanospheres. Interestingly, when the poor cosolvent is changed from water to MCH in THF, the chiral pattern remains unchanged, but the morphology changes completely. Supported by the collective spectroscopic and microscopic analysis, the present study efficaciously demonstrates the remarkable control of hydrophobic building block over the chiral sense and also highlights the fascinating influence of good as well as poor cosolvent in supporting the distinct molecular packing.

Background: With advancing age among older adults, the associated debilities increase, indicating a deteriorating health status as there is a gradual loss of muscle mass, strength, and functionality. Ayush Rasayana A and B are coded Ayurvedic medicines developed from herbal extracts. This study has been planned to prevent debilitating conditions and improve the quality of life (QOL) in older adults., Objective: This study aimed to assess the effectiveness of Ayush Rasayana A and B on the QOL, quality of sleep, and functionality of older adults, along with the tolerability of the intervention., Methods: This was a multicenter, open-label, cluster randomized controlled trial conducted with 720 participants aged 60 to 75 years. The participants were divided into 2 groups (intervention and control), with both receiving Ayurvedic ancillary treatment for 3 months. The intervention group additionally received 10 g of Ayush Rasayana A orally once daily at bedtime for 6 days, followed by 1.5 g of Ayush Rasayana B orally twice daily before food for the remaining 84 days. The assessment criteria included the Older People's Quality of Life Questionnaire Brief, Katz Index of Independence in Activities of Daily Living, Pittsburgh Sleep Quality Index, Five Times Sit-to-Stand Test, and shoulder and scapular movements. Any change in hematological and biochemical parameters and occurrence of treatment-emergent adverse events were also assessed during the study period., Results: The recruitment of the participants started in December 2023, and the final follow-up was completed in April 2024. Out of the total 720 enrolled participants, 686 (95.3%) completed the study up to the last follow-up., Conclusions: This study may provide evidence-based data to establish preventive treatment protocols for enhancing the QOL and functionality among older adults. The study results may also be helpful for the planning of interdisciplinary health policies for improving the health conditions of different populations., International Registered Report Identifier (irrid): DERR1-10.2196/58186., (©Pallavi Mundada, Deepa Makhija, Sunita Mata, Kalpana Kachare, Aparna Manathottathil, Abha Sharma, Bhogavalli Chandra Sekhara Rao, Rakesh Rana, Arunabh Tripathi, Kiran Rana, Vandana Joshi, Ashish Raturi, Anukampa Singh, N Srikanth, Rabinarayan Acharya. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.11.2024.)

Background/aims: Accurate assessment of disease activity is crucial for effective management and treatment of ulcerative colitis (UC). This study evaluated the correlation between clinical, endoscopic, and histologic measures of disease activity in UC., Methods: Clinical, biochemical, endoscopic, and histologic disease activity was studied in 347 patients with UC. Agreements among various histologic classification systems, namely the Geboes Score (GS), Continuous GS, Nancy Index (NI), and Robarts Histopathology Index (RHI), were analyzed. The predictive accuracy of fecal calprotectin (FC) for endoscopic and histologic remission was assessed., Results: We demonstrate a fair to moderate correlation between clinical, endoscopic, and histologic measures of disease activity in UC. There was a robust concordance among GS, Continuous GS, NI, and RHI in distinguishing between patients in histologic remission or activity. The NI detected 75% of patients who met the remission criteria according to the RHI, whereas the RHI identified all patients in remission as defined by the NI. FC levels below 150 μg/g had >70% accuracy in predicting endoscopic remission. FC levels below 150 μg/g showed ≥80% accuracy, and FC levels below 100 μg/g demonstrated ≥ 85% accuracy in predicting histologic remission, regardless of the scoring index applied. Elevated FC levels were associated with both acute and chronic inflammatory infiltrates in biopsy samples., Conclusions: FC is a reliable predictor of histologic remission, with higher accuracy at lower thresholds. The GS, Continuous GS, NI, and RHI demonstrate comparable performance. FC could help stratify patients' need for colonoscopy for the assessment of endoscopic and histologic remission.

Nanotheranostics, an amalgamation of therapeutic and diagnostic capabilities at the nanoscale, is revolutionizing personalized medicine. Polymer-drug conjugates (PDCs) stand at the forefront of this arena, offering a multifaceted approach to treat complex diseases such as cancer. This review explores the recent advancements in PDCs, highlighting their design principles, working mechanisms, and the therapeutic applications. We discuss the incorporation of imaging agents into PDCs that allow for real-time monitoring of drug delivery and treatment efficacy. With the aim of improving patient care, the review examines how PDCs enable targeted drug delivery, minimize side effects, and provide valuable diagnostic data, hence enhancing the precision of medical interventions. We also address the challenges facing the clinical translation of PDCs, such as scalability, regulatory hurdles, and cost-effectiveness, providing a comprehensive outlook on the future of nanotheranostics in patient management., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)