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Mycobacterium microti-infected mouse peritoneal microphages produced high amounts of prostaglandin E2 (PGE2) and nitric oxide (NO) when activated with interferon-γ (IFN-γ). In order to understand the relation between PGE2 and NO production and the expression of interleukin-12 (IL-12), interleukin-10 (IL-10) and MHC class-II (Ia) molecules by M. microti-infected and IFN-γ-stimulated macrophages, we analyzed the level of these molecules in the presence or absence of PGE2 and NO inhibitors. Addition of N G-methyl- l-arginine ( l-NMA) and indomethacin (IM) caused a significant increase in IL-12 level (2.6- and 1.9-fold, respectively) whereas IL-10 level decreased by 88 and 56%, respectively, relative to M. microti-infected and IFN-γ-treated control macrophages. Enhanced PGE2 and NO upregulated IL-10 expression and down-regulated IL-12 and MHC class-II (Ia) expression in M. microti-infected and IFN-γ-treated mouse peritoneal macrophages. [ABSTRACT FROM AUTHOR]

A strain of Micrococcus sp. was isolated for its capability of side chain degradation of cholesterol. This strain was characterized and identified as Micrococcus roseus. It was found to be the best strain for the production of androsta-1,4-diene-3, 17-dione and androst-4-ene-3, 17-dione compared with other Micrococcus strains. [ABSTRACT FROM AUTHOR]

A comparative study was done using J774A.1 and J774A. 1-derived transfected cells (J774A.1 C.1) containing antisense tumor necrosis factor α (TNF-α) plasmid to determine the role of endogenous TNF-α on nitric oxide production as well as on the growth of Mycobacterium microti in interferon γ (IFN-γ)- and lipopolysaccharide (LPS)-treated cells. On stimulation with IFN-γ and LPS a higher level of NO was observed in J774A.1 cells compared to J774A.1 C.1 which indicated that endogenous TNF-α is required for the production of NO. Comparing the effect of IFN-γ and LPS on the intracellular growth of M. microti, the growth-reducing activity was higher in J774A.1 cells than in J774A.1 C.1 cells and was not completely abrogated in the presence of the nitric oxide inhibitor N G-methyl- l-arginine ( l-NMA). J774A.1 C.1 cells infected with M. microti produced a significant amount of NO when exogenous TNF-α was added along with IFN-γ and LPS and the concentration of intracellular bacteria decreased almost to that in IFN-γ and LPS treated parental J774A.1 cells. Addition of exogenous TNF-α even in the presence of l-NMA in J774.1 C.1 cells could also partially restore intracellular growth inhibition of M. microti caused by IFN-γ and LPS. TNF-α is probably required for the production of NO in J774A.1 cells by IFN-γ and LPS but TNF-α and NO are independently involved in the killing of intracellular M. microti with IFN-γ and LPS. [ABSTRACT FROM AUTHOR]

Lichen scrofulosorum is a tuberculid that is usually seen in children or young adults. Although a rare occurrence, this tuberculid is an important marker of occult tuberculosis, which may not be detected otherwise. We report here a case of lichen scrofulosorum in a ten year-old boy with typical grouped lichenoid papules on the trunk associated with axillary tuberculous lymphadenitis.

Abstract Background There is considerable ambiguity in the subjective dimensions that comprise much of the relational dynamic of the clinical encounter. Comfort with this ambiguity, and recognition of the potential uncertainty of particular domains of medicine (e.g. – cultural factors of illness expression, value bias in diagnoses, etc) is an important facet of medical education. This paper begins by defining ambiguity and uncertainty as relevant to clinical practice. Studies have shown differing patterns of students' tolerance for ambiguity and uncertainty that appear to reflect extant attitudinal predispositions toward technology, objectivity, culture, value- and theory-ladeness, and the need for self-examination. This paper reports on those findings specifically related to the theme of uncertainty as relevant to teaching about cultural diversity. Its focus is to identify how and where the theme of certainty arose in the teaching and learning of cultural diversity, what were the attitudes toward this theme and topic, and how these attitudes and responses reflect and inform this area of medical pedagogy. Methods A semi-structured interview was undertaken with 61 stakeholders (including policymakers, diversity teachers, students and users). The data were analysed and themes identified. Results There were diverse views about what the term cultural diversity means and what should constitute the cultural diversity curriculum. There was a need to provide certainty in teaching cultural diversity with diversity teachers feeling under considerable pressure to provide information. Students discomfort with uncertainty was felt to drive cultural diversity teaching towards factual emphasis rather than reflection or taking a patient centred approach. Conclusion Students and faculty may feel that cultural diversity teaching is more about how to avoid professional, medico-legal pitfalls, rather than improving the patient experience or the patient-physician relationship. There may be pressure to imbue cultural diversity issues with levels of objectivity and certainty representative of other aspects of the medical curriculum (e.g. – biochemistry). This may reflect a particular selection bias for students with a technocentric orientation. Inadvertently, medical education may enhance this bias through training effects, and accommodate disregard for subjectivity, over-reliance upon technology and thereby foster incorrect assumptions of objective certainty. We opine that it is important to teach students that technology cannot guarantee certainty, and that dealing with subjectivity, diversity, ambiguity and uncertainty is inseparable from the personal dimension of medicine as moral enterprise. Uncertainty is inherent in cultural diversity so this part of the curriculum provides an opportunity to address the issue as it relates to pateint care.

Abstract Background Cultural diversity teaching is increasingly present in both undergraduate and postgraduate training programmes. This study explored the views of stakeholders in medical education about the potential outcomes of cultural diversity teaching and how they thought cultural diversity programmes might be effectively evaluated. Methods A semi-structured interview was undertaken with 61 stakeholders (including policymakers, diversity teachers, students and users). The data were analysed and themes identified. Results Many participants felt that clinical practice was improved through 'cultural diversity teaching' and this was mostly as a result of improved doctor-patient communication. There was a strong view that service users need to participate in the evaluation of outcomes of cultural diversity teaching. Conclusion There is a general perception, rather than clear evidence, that cultural diversity teaching can have a positive effect on clinical practice. Cultural diversity teaching needs to be reviewed in undergraduate and postgraduate medicine and better evaluation tools need to be established.

Use of online sources to track disease outbreaks and deliver real-time surveillance in emerging public health threats is becoming the need of the hour as resurgence of diseases challenge global health systems. Recent advances in Geographical Information System (GIS) and mapping technologies have enhanced diseases surveillance programs. The current paradigm shifts are moving towards greater adoption of the ubiquitous internet for GIS deployment. This paper attempts to highlight the applicability of three online disease mapping tools - Google trends (GT), HealthMap and Kazemill as newer paradigms of disease surveillance in India. The study has been limited to comparing the trends obtained from the online tools with freely available public health data for few diseases such as malaria, typhoid and cholera that commonly occur in India. We conclude that G T could possibly be used for providing first hand information of impending disease outbreaks subject to further validation against past trends of the disease to have more relevance. [ABSTRACT FROM AUTHOR]

Stress shielding in dental and orthopedic implants is a long-standing hurdle, and trabecular porous architecture to improve bone ingrowth is deemed to be a potential solution. Fabricating Ti 6 Al 4 V components with dense-porous bilayer structures is complicated with limited lab-scale and commercial success. Here, a green dough-forming technique with metal powders is successfully explored to develop heterogeneous structures with a monolith-like dense-porous interface. The porous region achieved 70% porosity with a 25 MPa compressive strength comparable to human cancellous bone. Due to its simplicity and versatility, this process is a promising solution for developing and mass-manufacturing customized designs for bone-related implants with improved bone ingrowth and osseointegration.

Glioblastoma (GBM) is the highest grade of glioma for which no effective therapy is currently available. Despite extensive research in diagnosis and therapy, there has been no significant improvement in GBM outcomes, with a median overall survival continuing at a dismal 15-18 months. In recent times, glioblastoma stem cells (GSCs) have been identified as crucial drivers of treatment resistance and tumor recurrence, and GBM therapies targeting GSCs are expected to improve patient outcomes. We used a multistep in silico screening strategy to identify repurposed candidate drugs against selected therapeutic molecular targets in GBM with potential to concomitantly target GSCs. Common differentially expressed genes (DEGs) were identified through analysis of multiple GBM and GSC datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). For identification of target genes, we selected the genes with most significant effect on overall patient survival. The relative mRNA and protein expression of the selected genes in TCGA control versus GBM samples was also validated and their cancer dependency scores were assessed. Drugs targeting these genes and their corresponding proteins were identified from LINCS database using Connectivity Map (CMap) portal and by in silico molecular docking against each individual target using FDA-approved drug library from the DrugBank database, respectively. The molecules thus obtained were further evaluated for their ability to cross blood brain barrier (BBB) and their likelihood of resulting in drug resistance by acting as p-glycoprotein (p-Gp) substrates. The growth inhibitory effect of these final shortlisted compounds was examined on a panel of GBM cell lines and compared with temozolomide through the drug sensitivity EC50 values and AUC from the PRISM Repurposing Secondary Screen, and the IC50 values were obtained from GDSC portal. We identified RPA3, PSMA2, PSMC2, BLVRA, and HUS1 as molecular targets in GBM including GSCs with significant impact on patient survival. Our results show GSK-2126458/omipalisib, linifanib, drospirenone, eltrombopag, nilotinib, and PD198306 as candidate drugs which can be further evaluated for their anti-tumor potential against GBM. Through this work, we identified repurposed candidate therapeutics against GBM utilizing a GSC inclusive targeting approach, which demonstrated high in vitro efficacy and can prospectively evade drug resistance. These drugs have the potential to be developed as individual or combination therapy to improve GBM outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes in patients with metastatic castration-resistant prostate cancer. Previous work showed that dynamic interconversions between epithelial-mesenchymal transition to mesenchymal-epithelial transition defines the phenotypic landscape of prostate tumors, as a potential driver of the emergence of therapeutic resistance. In this study, we use in vitro and in vivo preclinical MDA PCa patient-derived xenograft models of resistant human prostate cancer to determine molecular mechanisms of cross-resistance between antiandrogen therapy and taxane chemotherapy, underlying the therapeutically resistant phenotype. Transcriptomic profiling revealed that resistant and sensitive prostate cancer C4-2B cells have a unique differential gene signature response to cabazitaxel. Gene pathway analysis showed that sensitive cells exhibit an increase in DNA damage, while resistant cells express genes associated with protein regulation in response to cabazitaxel. The patient-derived xenograft model specimens are from patients who have metastatic lethal castration-resistant prostate cancer, treated with androgen deprivation therapy, antiandrogens, and chemotherapy including second-line taxane chemotherapy, cabazitaxel. Immunohistochemistry revealed high expression of E-cadherin and low expression of vimentin resulting in redifferentiation toward an epithelial phenotype. Furthermore, the mitotic kinesin-related protein involved in microtubule binding and the SLCO1B3 transporter (implicated in cabazitaxel intracellular transport) are associated with resistance in these prostate tumors. Combinational targeting of kinesins (ispinesib) with cabazitaxel was more effective than single monotherapies in inducing cell death in resistant prostate tumors. Implications: Our findings are of translational significance in identifying kinesin as a novel target of cross-resistance toward enhancing therapeutic vulnerability and improved clinical outcomes in patients with advanced prostate cancer., (©2024 American Association for Cancer Research.)

From eukaryotes to prokaryotes, all cells secrete extracellular vesicles (EVs) as part of their regular homeostasis, intercellular communication, and cargo disposal. Accumulating evidence suggests that small EVs carry functional small RNAs, potentially serving as extracellular messengers and liquid-biopsy markers. Yet, the complete transcriptomic landscape of EV-associated small RNAs during disease progression is poorly delineated due to critical limitations including the protocols used for sequencing, suboptimal alignment of short reads (20-50 nt), and uncharacterized genome annotations-often denoted as the 'dark matter' of the genome. In this study, we investigate the EV-associated small unannotated RNAs that arise from endogenous genes and are part of the genomic 'dark matter', which may play a key emerging role in regulating gene expression and translational mechanisms. To address this, we created a distinct small RNAseq dataset from human prostate cancer & benign tissues, and EVs derived from blood (pre- & post-prostatectomy), urine, and human prostate carcinoma epithelial cell line. We then developed an unsupervised data-based bioinformatic pipeline that recognizes biologically relevant transcriptional signals irrespective of their genomic annotation. Using this approach, we discovered distinct EV-RNA expression patterns emerging from the un-annotated genomic regions (UGRs) of the transcriptomes associated with tissue-specific phenotypes. We have named these novel EV-associated small RNAs as 'EV-UGRs' or "EV-dark matter". Here, we demonstrate that EV-UGR gene expressions are downregulated by ∼100 fold (FDR < 0.05) in the circulating serum EVs from aggressive prostate cancer subjects. Remarkably, these EV-UGRs expression signatures were regained (upregulated) after radical prostatectomy in the same follow-up patients. Finally, we developed a stem-loop RT-qPCR assay that validated prostate cancer-specific EV-UGRs for selective fluid-based diagnostics. Overall, using an unsupervised data driven approach, we investigate the 'dark matter' of EV-transcriptome and demonstrate that EV-UGRs carry tissue-specific Information that significantly alters pre- and post-prostatectomy in the prostate cancer patients. Although further validation in randomized clinical trials is required, this new class of EV-RNAs hold promise in liquid-biopsy by avoiding highly invasive biopsy procedures in prostate cancer., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

It is known that small extracellular vesicles (sEVs) are released from cancer cells and contribute to cancer progression via crosstalk with recipient cells. We have previously reported that sEVs expressing the αVβ3 integrin, a protein upregulated in aggressive neuroendocrine prostate cancer (NEPrCa), contribute to neuroendocrine differentiation (NED) in recipient cells. Here, we examine the impact of αVβ3 expression on sEV protein content, density and function. sEVs used in this study were isolated by iodixanol density gradients and characterized by nanoparticle tracking analysis, immunoblotting and single vesicle analysis. Our proteomic profile of sEVs containing αVβ3 shows downregulation of typical effectors involved in apoptosis and necrosis and an upregulation of tumour cell survival factors compared to control sEVs. We also show that the expression of αVβ3 in sEVs causes a distinct reposition of EV markers (Alix, CD81, CD9) to a low-density sEV subpopulation. This low-density reposition is independent of extracellular matrix (ECM) protein interactions with sEVs. This sEV subset contains αVβ3 and an αVβ3 downstream effector, NgR2, a novel marker for NEPrCa. We show that sEVs containing αVβ3 are loaded with higher amounts of NgR2 as compared to sEVs that do not express αVβ3. Mechanistically, we demonstrate that sEVs containing NgR2 do not affect the sEV marker profile, but when injected in vivo intratumorally, they promote tumour growth and induce NED. We show that sEVs expressing NgR2 increase the activation of focal adhesion kinase (FAK), a known promoter of cancer cell proliferation, in recipient cells. We also show that NgR2 mimics the effect of sEVs containing αVβ3 since it displays increased growth of NgR2 transfectants in vivo, as compared to control cells. Overall, our results describe the changes that occur in cargo, density and functions of cancer cell-derived sEVs containing the αVβ3 integrin and its effector, NgR2, without affecting the sEV tetraspanin profiles., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Background/objectives: Stroke damage to the primary visual cortex induces large, homonymous visual field defects that impair daily living. Here, we asked if vision-related quality of life (VR-QoL) is impacted by time since stroke., Subjects/methods: We conducted a retrospective meta-analysis of 95 occipital stroke patients (female/male = 26/69, 27-78 years old, 0.5-373.5 months poststroke) in whom VR-QoL was estimated using the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ) and its 10-item neuro-ophthalmic supplement (Neuro10). Visual deficit severity was represented by the perimetric mean deviation (PMD) calculated from 24-2 Humphrey visual fields. Data were compared with published cohorts of visually intact controls. The relationship between VR-QoL and time poststroke was assessed across participants, adjusting for deficit severity and age with a multiple linear regression analysis., Results: Occipital stroke patients had significantly lower NEI-VFQ and Neuro10 composite scores than controls. All subscale scores describing specific aspects of visual ability and functioning were impaired except for ocular pain and general health, which did not differ significantly from controls. Surprisingly, visual deficit severity was not correlated with either composite score, both of which increased with time poststroke, even when adjusting for PMD and age., Conclusions: VR-QoL appears to improve with time postoccipital stroke, irrespective of visual deficit size or patient age at insult. This may reflect the natural development of compensatory strategies and lifestyle adjustments. Thus, future studies examining the impact of rehabilitation on daily living in this patient population should consider the possibility that their VR-QoL may change gradually over time, even without therapeutic intervention., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Extracellular matrix (ECM) rich whole organ bio-scaffolds, preserving structural integrity and essential growth factors, has potential towards regeneration and reconstruction. Women with cervical anomalies or trauma can benefit from clinical cervicovaginal repair using constructs rich in site specific ECM. In this study, complete human cervix decellularization was achieved using a modified perfusion-based stir bench top decellularization method. This was followed by physico-chemical processes including perfusion of ionic agents, enzymatic treatment and washing using detergent solutions for a duration of 10-12 d. Histopathological analysis, as well as DNA quantification confirmed the efficacy of the decellularization process. Tissue ultrastructure integrity was preserved and the same was validated via scanning electron microscopy and transmission electron microscopy studies. Biochemical analysis and structural characterizations like Fourier transform infrared, Raman spectroscopy of decellularized tissues demonstrated preservation of important proteins, crucial growth factors, collagen, and glycosaminoglycans. In vitro studies, using THP-1 and human umbilical vein endothelial cell (HUVEC) cells, demonstrated macrophage polarization from M1 to M2 and vascular functional genes enhancement, respectively, when treated with decellularized human cervical matrix (DHCp). Crosslinked DHC scaffolds were recellularized with site specific human cervical epithelial cells and HUVEC, showing non-cytotoxic cell viability and enhanced proliferation. Furthermore, DHC scaffolds showed immunomodulatory effects in vivo on small rodent model via upregulation of M2 macrophage genes as compared to decellularized rat cervix matrix scaffolds (DRC). DHC scaffolds underwent neo-vascularization followed by ECM remodeling with enhanced tissue integration., (© 2024 IOP Publishing Ltd.)

Objective: Development and test of a culturally sensitive intervention for rheumatology healthcare professionals (HCPs)., Methods: Using a before and after study design, 15 HCPs were recruited to undertake the bespoke intervention from four National Health Service sites across England, in areas serving a diverse population. The intervention was evaluated using two validated outcomes: (i) Patient Reported Physician Cultural Competency (PRPCC); and (ii) Patient Enablement Instrument (PEI), measuring patients' perceptions of their overall healthcare delivery. Additionally, HCPs completed the COM-B questionnaire for capability (C), opportunity (O) and motivation (M) to perform behaviour (B), measuring behaviour change., Results: Two hundred patients were recruited before HCPs undertook the intervention (cohort 1), and 200 were recruited after (cohort 2) from 15 HCPs; after exclusions 178 patients remained in cohort 1 and 186 in cohort 2. Sixty percent of patients identified as white in both recruited cohorts, compared with 29% and 33% of patients (cohorts 1 and 2, respectively) who identified as being of South Asian origin. After the intervention, the COM-B scores indicated that HCPs felt more skilled and equipped for consultations. No significant differences were noted in the average overall cultural competency score between the two cohorts in white patients (57.3 vs 56.8, P = 0.8), however in the South Asian cohort there was a statistically significant improvement in mean scores (64.1 vs 56.7, P = 0.014). Overall, the enablement score also showed a statistically significant improvement following intervention (7.3 vs 4.3, P < 0.001) in the white patients and in the South Asian patients (8.0 vs 2.2, P < 0.001)., Conclusion: This novel study provides evidence for improving cultural competency and patient enablement in rheumatology settings., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To evaluate and compare pharyngeal airway and tongue space changes after treatment with fixed functional appliances-Herbst and AdvanSync™ (Ormco, Orange, CA, USA) appliances-in skeletal class II patients in pre- and posttreatment lateral cephalograms., Methods: For this randomized, controlled trial, 40 patients (21 male, 19 female) were divided into two groups-a Herbst group (mean age 12.6 ± 0.67 years) and an AdvanSync group (mean age 12.8 ± 0.66 years). Pre- and posttreatment (appliance therapy duration-8 months) lateral cephalograms were traced using a software program to evaluate pharyngeal airway and tongue space changes., Results: Nasopharyngeal airway, velopharyngeal airway, glossopharyngeal airway, and hypopharyngeal airway increased in the Herbst group by 2.12 mm (p ≤ 0.001), 2.33 mm (p ≤ 0.001), 2.40 mm (p ≤ 0.01), and 1.57 mm (p ≤ 0.05), while in the AdvanSync group the increases were 1.89 mm (p ≤ 0.001), 1.21 mm (p ≤ 0.001), 1.18 mm (p ≤ 0.001), and 1.53 mm (p ≤ 0.001), respectively. In the Herbst group, tongue length and height increases were 2.04 mm (p ≤ 0.01) and 3.74 mm (p ≤ 0.001), while the values in the AdvanSync group were 2.41 mm (p ≤ 0.05) and 2.69 mm (p ≤ 0.001). The change of the tongue tip from the lower occlusal plane was 0.69 mm (p ≤ 0.001) in the Herbst group and 0.77 mm (p ≤ 0.001) in the AdvanSync group. The velopharyngeal airway dimension was correlated positively with that of the retroglossal oropharyngeal airway, which in-turn positively correlated with the laryngopharyngeal airway which correlated well with the distance of the tongue tip from the lower occlusal plane., Conclusions: The airway dimensions and tongue parameters increased significantly in both treatment groups in the present study. These changes were higher in the Herbst appliance than in the AdvanSync group, except for the distance of the tongue tip from the lower occlusal plane. A significant difference between the pharyngeal airways was found only for the retropalatal oropharyngeal airway., (© 2023. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Chronic wounds suffer from impaired healing due to microbial attack and poor vascular growth. Thermoresponsive hydrogels gained attention in wound dressing owing to their gelation at physiological temperature enabling them to take the shape of asymmetric wounds. The present study delineates the development of thermoresponsive hydrogel (MCK), from hair-derived keratin (K) and methylcellulose (MC) in the presence of sodium sulfate. The gelation temperature (T g ) of this hydrogel is in the range of 30 °C to 33 °C. Protein-polymer interaction leading to thermoreversible sol-gel transition involved in MCK blends has been analyzed and confirmed by FTIR, XRD, and thermal studies. Keratin, has introduced antioxidant properties to the hydrogel imparted cytocompatibility towards human dermal fibroblasts (HDFs) as evidenced by both MTT and live dead assays. In vitro wound healing assessment has been shown by enhanced migration of HDFs in the presence of MCK hydrogel compared to the control. Also, CAM assay and CD31 expression by the Wistar rat model has shown increased blood vessel branching after the implantation of MCK hydrogel. Further, in vivo study, demonstrated MCK efficacy of hydrogel in accelerating full-thickness wounds with minimal scarring in Wistar rats, re-epithelialization, and reinstatement of the epidermal-dermal junction thereby exhibiting clinical relevance for chronic wounds., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Context: Anastomotic leak after primary repair of esophageal atresia (EA) with tracheoesophageal fistula (TEF) is a well-known complication and can represent a challenging clinical scenario., Aims: The present study aimed to evaluate the role of glycopyrrolate as an adjunct in the treatment of anastomotic leak after primary repair of EA Vogt type 3b., Settings and Design: A retrospective study was carried out in our tertiary care teaching institute from January 2015 to December 2022., Materials and Methods: Neonates with EA with distal TEF with primary repair who had developed anastomotic leak, managed by the author(s), were studied. The study included patients with major, minor, and radiological leaks. Glycopyrrolate was administered in the dose of 4 μg/kg 8 hourly. The outcomes of the study were either resolution or progression of the leak., Results: There were 21 patients who were managed with glycopyrrolate in addition to the classical treatment of the anastomotic leak following repair of EA with distal TEF. The male: female ratio was 1:1.1. All the cases had anastomotic leaks with either clinically detectable in the chest tube (15) or radiological leak (6). The leaks were detected early in patients with major leak (mean = 3.2 ± 0.84 days) compared to minor leak (mean =4.9 ± 1.29 days). Radiological leaks were detected in all the neonates on postoperative day 7. In five patients with major leak, there was a negligible reduction in the amount of chest tube output, and were subjected to diversion procedures. There were a total of three deaths out of five in this group. In 10 patients with minor leak, there was complete resolution of anastomotic leak in eight patients (80%); there was one patient each with mortality and diversion procedure. The patients with a radiological leak (6) did not show any deterioration, and they were fed 1-5 days after the esophagogram., Conclusions: Glycopyrrolate may be an advantageous postoperative adjunct in the management of minor and radiological leak after tracheoesophageal repair., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Indian Association of Pediatric Surgeons.)

A Thyroglossal cyst is a commonly encountered clinical entity resulting due to the persistence of the thyroglossal duct and the transformation of a few embryonic cells into a cyst. The incidence of malignant change in the thyroglossal cyst is reported as between 1 to 1.8 percent. Here we present a case report of a male who presented with swelling in the neck, on ultrasonography (USG) found to be a thyroglossal cyst, fine needle aspiration cytology (FNAC) suggested a papillary carcinoma within the thyroglossal cyst. Total thyroidectomy with bilateral selective neck dissection, central compartment clearance, and sistrunk operation were done. The histopathological report revealed papillary carcinoma of the thyroid within a thyroglossal cyst with neck nodal metastasis., Competing Interests: Conflict of interestNil., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

FABP3 belongs to a large family of cytoplasmic fatty acid binding proteins that are expressed in a tissue-specific manner. It is predominantly expressed in breast, muscle and heart. During our exploratory studies on the role of FABP3 in tumorigenesis and our consequent attempts to study the molecular mechanism responsible for the oncogenic potential of FABP3, we came across an unexpected role of FABP3 as an anti-bacterial protein. Presence of the protein was detected in culture media of cell lines stably over-expressing human FABP3. Conditioned medium from these FABP3 over-expressing cells exerted a distinct anti-bacterial activity against E. coli. Our results indicate that binding of FABP3 to the bacterial cell surface contributes to its anti-bacterial activity. Incubation of E. coli bacterial cells with FABP3 protein led to disruption of the physical integrity of bacterial cell membrane causing leakage of cellular components. Further, in silico analysis predicted strong binding of FABP3 to the antibiotic binding sites on the bacterial ribosome. Interestingly, we found that FABP3 is a naturally occurring secretory protein present in milk in abundance as confirmed by western blot and ELISA. Thus, our experimental data together with in silico analysis suggests that FABP3 is secreted in milk, has an anti-bacterial function, shows activity against E. coli by disrupting bacterial membrane and targeting the ribosome, and may play a protective role against bacterial infection in newborns., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Whey protein-derived carbon nanodots (WCND) were synthesized using the microwave irradiation method, and its amine-rich surface functionality was crosslinked with covalently bound Iodine functionalized 2,5-dimethoxy-2,5-dihydrofuran (DHFI) to produce WCND-DHFI. The physicochemical characterization of both WCND and WCND-DHFI was performed and compared to comprehend the consequence of iodination on the characteristics of WCND. The suitability of CND in biological environments was evaluated through in vitro cytocompatibility and Chorioallantoic Membrane (CAM) assay, as well as a hemocompatibility study. WCND-DHFI has shown enhanced cell viability against WCND. Further, the antibacterial properties of both CNDs were studied against both gram-positive and gram-negative bacterial strains, representing an enhancement in antibacterial activity after DHFI crosslinking. WCND-DHFI has depicted a stable and prominent bacteriostatic activity for up to 6 h for both strains of bacteria. WCND-DHFI has denoted a 99.996% and 99.999% loss of bacterial viability for gram-positive and negative strains, respectively. Novel surface functionalization portrays an improvement in antibacterial activity. Transmission and scanning electron microscopy represent the cell wall rupturing by the WCND-DHFI, resulting in bacterial death. The ROS-mediated bacteriostatic mechanism of WCND-DHFI has been explored through assessing lipid peroxidation and protein oxidation assay. Moreover, the oxidative damage of DNA also has been explored. WCND-DHFI is performing as a promising cytocompatible and hemocompatible material for antibacterial applications., 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 © 2023 Elsevier B.V. All rights reserved.)

Junk foods are typically low in essential nutrients, such as vitamins, minerals, and antioxidants. They are also loaded with trans fats and saturated fats, which can increase the level of triglycerides in the blood. High triglyceride levels can contribute to the development of non-alcoholic fatty liver disease (NAFLD), a condition where excess fat accumulates in the liver. A high intake of junk foods can lead to insulin resistance, a condition where the body's cells become less responsive to insulin. A diet lacking in nutrients and loaded with unwanted toxins can impair the liver's ability to detoxify harmful substances and damage its overall function. It is known that the regular consumption of junk food can be linked to memory impairment and cognitive decline. Several studies have shown that diets high in unhealthy fats, sugars, and processed foods can negatively impact brain health, including memory function. In this study, Wistar rats were used to model Late-Onset Alzheimer's Disease (LOAD), which was inspired by knowledge of the liver-brain axis's role in causing dementia. The model mimicked junk-food-induced liver-brain damage, and was developed by using the toxins d-galactosamine, ethanol and d-galactose. To begin with, the model rats demonstrated insulin resistance, a characteristic of LOAD patients. Glucose levels in both the brain and liver tissues were significantly elevated in the model, paralleling clinical findings in LOAD patients. High glucose levels in the brain lead to the increased production of advanced glycation end-products (AGEs), which, along with amyloid beta, harm neighbouring neurons. Histopathological analysis revealed deformed glial nodules, apoptotic neurons, and amyloid plaques in the brain section in the later stages of the disease. Simultaneously, the liver section displayed features of cirrhosis, including an effaced lobular architecture and the extravasation of red blood cells. Liver enzymes ALT, AST and ALP were consistently elevated with disease progression. Furthermore, immunohistochemistry confirmed the presence of amyloid precursor protein (APP) in the diseased brain. The positive expression of Hypoxia-Inducible Factor 3-Alpha (HIF3A) in the brain indicated hypoxic conditions, which is consistent with other LOAD studies. This model also exhibited damaged intestinal villi and excessive bowel and urinary incontinence, indicating malnutrition and a disturbed gut microbiome, which is also consistent with LOAD patients. Bioinformatics analysis on serum protein suggests a few affected molecular pathways, like the amyloid secretase pathway, androgen/oestrogen/progesterone biosynthesis, the apoptosis signalling pathway, the insulin/IGF pathway-protein kinase B signalling cascade, the Metabotropic glutamate receptor group I pathway, the Wnt signalling pathway, etc. Behavioural analysis confirmed memory decline and the loss of muscle strength with disease progression. Overall, this rat model of LOAD sheds valuable light on LOAD pathology and highlights the potential link between liver dysfunction, particularly induced by the excessive consumption of junk food, and LOAD. This study contributes to a deeper understanding of the complex molecular mechanisms involved in LOAD, paving the way for new possibilities in therapeutic interventions.

Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.

Objective: The goal of this article was to describe trends in publications (including conference abstracts) and clinical trials that report on glycemic time in range (TIR)., Data Sources: Reviewed databases included but were not limited to MEDLINE and Embase. Clinical trial registries were also sourced., Study Selection: All studies reporting TIR published between 2010 and 2021 were included. Clinical trials reporting TIR that started in or after 2010 were also included. Non-English publications, abstracts, and clinical trials were excluded. Book chapters, nonhuman studies, and studies not reporting TIR were excluded., Data Extraction: Manuscript/abstract category, publication year, study region, interventional versus observational role of continuous glucose monitoring (CGM), and clinical trial start and completion dates were captured. Glycemic outcomes reported in publications or trials, including TIR as a primary outcome, A1C, time below range (TBR), and time above range (TAR), were also captured., Results: A total of 373 clinical trials, 531 publications, and 620 abstracts were included in the review. The number of trials, publications, and abstracts reporting TIR significantly increased, particularly between 2018 and 2021, during which time the number of clinical trials, publications, and conference abstracts reporting TIR increased by 6-fold, 12-fold, and 4.5-fold, respectively. About 35-44% of studies reported TIR as a primary outcome. Approximately 54% of clinical trials, 47% of publications, and 47% of conference abstracts reported the role of CGM to be observational. TBR was reported more often than TAR., Conclusion: The marked increase in the number of trials, publications, and abstracts reporting TIR highlights the increasing significance and acceptance of TIR as an outcome measure in diabetes management., Competing Interests: P.M.P. was an employee of Abbott Diabetes Care during the study. R.M.A., N.D., C.B.L., M.A.F., and N.S.V. are employees of Abbott Diabetes Care. No other potential conflicts of interest relevant to this article were reported., (© 2023 by the American Diabetes Association.)

Herein, we present, a chemiresistive-type gas sensor composed of two-dimensional 1T-2H phase MoSe 2 and MoO 3 . Mixed phase MoSe 2 and MoSe 2 /MoO 3 composites were synthesized via a facile hydrothermal method. The structure analysis using X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy revealed the formation of different phases of MoSe 2 at different temperatures. With increase in synthesis temperature from 180 to 200 °C, the relative percentage of 1T and 2H-MoSe 2 phases changed from 80 to 48%. On the other hand, at 220 °C, 2H-MoSe 2 was obtained as a major component. The gas sensing properties of individual MoSe 2 and composites were investigated at room temperature toward various analytes. The obtained results revealed that composites possess improved sensing features as compared with individual MoSe 2 or MoO 3 . Data also revealed that the composite with dominating 1T-phase exhibits relatively higher response (10%, at 10 ppm) for dimethylformamide (DMF) compared to triethylamine (TEA) (3%, at 10 ppm). In contrast, the composite with larger 2H-phase exhibited affinity toward TEA and had a relative response of about 2%. Therefore, selectivity of a sensor device can be tuned by an appropriately designed MoSe 2 /MoO 3 composite. These results signify the importance of MoO 3 -based composites with dual-phase MoSe 2 for successfully discriminating between DMF and TEA at room-temperature.

Cervical atresia is a rare congenital Müllerian duct anomaly that manifests as the absence or deformed nonfunctional presence of the cervix. Herein, a multi-layered biodegradable stent is fabricated using a homogeneous blend of silk fibroin with polycaprolactone using hexafluoroisopropanol as a common solution. Briefly, a concentric cylinder of 3D honeycomb layer is sandwiched within electrospun sheets for fixing at the cervico-uterine junction to pave the way of cervical reconstruction. An average length of 40 mm with 3 mm diameter is fabricated for the hybrid stent design. SEM evidences an evenly distributed pore architecture of the electrospun layer, and mechanical characterization of stent reveals a tensile strength of 1.7 ± 0.2 MPa, with a Young's modulus of 5.9 ± 0.1 MPa. Physico-chemical characterization confirms the presence of silk fibroin and poly caprolactone within the engineered stent. Following 14 days of pepsin enzymatic degradation, 18% degradation and a contact angle measurement of 97° are observed. In vitro cytocompatibility studies are performed using site-specific primary human cervical squamous, columnar epithelial cells, and human endometrial stromal cells. The study demonstrates non-cytotoxic cells' viability (no significant toxicity), improved cell anchoring, adherence among the stent layers, and proliferation in the 3D microenvironment. Furthermore, in vivo subcutaneous studies in the rodent model indicate that the implanted stent undergoes constructive remodeling, neo-tissue creation, neo-vasculature formation, and re-epithelialization while maintaining patency for 2 months.

Background: Adeno-associated virus (AAV) has emerged as one of the best tools for cardiac gene delivery due to its cardiotropism, long-term expression, and safety. However, a significant challenge to its successful clinical use is preexisting neutralizing antibodies (NAbs), which bind to free AAVs, prevent efficient gene transduction, and reduce or negate therapeutic effects. Here we describe extracellular vesicle-encapsulated AAVs (EV-AAVs), secreted naturally by AAV-producing cells, as a superior cardiac gene delivery vector that delivers more genes and offers higher NAb resistance., Methods: We developed a 2-step density-gradient ultracentrifugation method to isolate highly purified EV-AAVs. We compared the gene delivery and therapeutic efficacy of EV-AAVs with an equal titer of free AAVs in the presence of NAbs, both in vitro and in vivo. In addition, we investigated the mechanism of EV-AAV uptake in human left ventricular and human induced pluripotent stem cell-derived cardiomyocytes in vitro and mouse models in vivo using a combination of biochemical techniques, flow cytometry, and immunofluorescence imaging., Results: Using cardiotropic AAV serotypes 6 and 9 and several reporter constructs, we demonstrated that EV-AAVs deliver significantly higher quantities of genes than AAVs in the presence of NAbs, both to human left ventricular and human induced pluripotent stem cell-derived cardiomyocytes in vitro and to mouse hearts in vivo. Intramyocardial delivery of EV-AAV9-sarcoplasmic reticulum calcium ATPase 2a to infarcted hearts in preimmunized mice significantly improved ejection fraction and fractional shortening compared with AAV9-sarcoplasmic reticulum calcium ATPase 2a delivery. These data validated NAb evasion by and therapeutic efficacy of EV-AAV9 vectors. Trafficking studies using human induced pluripotent stem cell-derived cells in vitro and mouse hearts in vivo showed significantly higher expression of EV-AAV6/9-delivered genes in cardiomyocytes compared with noncardiomyocytes, even with comparable cellular uptake. Using cellular subfraction analyses and pH-sensitive dyes, we discovered that EV-AAVs were internalized into acidic endosomal compartments of cardiomyocytes for releasing and acidifying AAVs for their nuclear uptake., Conclusions: Together, using 5 different in vitro and in vivo model systems, we demonstrate significantly higher potency and therapeutic efficacy of EV-AAV vectors compared with free AAVs in the presence of NAbs. These results establish the potential of EV-AAV vectors as a gene delivery tool to treat heart failure., Competing Interests: Disclosures None.