Bladder-resident bacteria associated with increased risk of recurrence after electrofulguration in women with antibiotic-recalcitrant urinary tract infection.

Background: Antibiotic-recalcitrant recurrent urinary tract infection (rUTI) is has become increasingly observed in postmenopausal women. Therefore, when standard antibiotic therapies have failed, some elect electrofulguration (EF) of areas of chronic cystitis when detected on office cystoscopy. EF is thought to remove tissue-resident bacteria that have been previously detected in the bladder walls of postmenopausal women with rUTI. We hypothesized that increased bladder bacterial burden may be associated with incomplete rUTI resolution following EF. Methods: Following IRB approval, bladder biopsies were obtained from 34 consenting menopausal women electing EF for the advanced management of rUTI. 16S rRNA FISH was performed using both universal and Escherichia probes and tissue-resident bacterial load was quantified. Time to UTI relapse after EF was recorded during a six-month follow-up period and the association of bladder bacterial burden and clinical covariates with UTI relapse was assessed. Results: We observed bladder-resident Escherichia in 52% of all participants and in 92% of participants with recent E. coli UTI. Time-to-relapse analysis revealed that women with high bladder bacterial burden as detected by the universal probe had a significantly ( p =0.035) higher risk of UTI within six months of EF (HR=3.15, 95% CI: 1.09-9.11). Interestingly, bladder-resident Escherichia was not significantly associated ( p =0.26) with a higher risk of UTI relapse (HR= 2.14, 95% CI: 0.58-7.90). Conclusions: We observed that total bladder bacterial burden was associated with a 3.1x increased risk of rUTI relapse within six months. Continued analysis of the relationship between bladder bacterial burden and rUTI outcomes may provide insight into the management of these challenging patients.

Factor Xa inhibitors versus low-molecular-weight heparin for preventing coagulopathy following COVID-19: a systematic review and meta-analysis of randomized controlled trials.

Background: Hospitalized patients with COVID-19 have shown a significant occurrence of thromboembolism and a heightened risk of death. It remains unclear whether factor Xa inhibitors are superior to enoxaparin in this context. Hence, there is a need for a direct comparison to assess the preventive effects and safety of factor Xa inhibitors versus enoxaparin in hospitalized COVID-19 patients. Methods: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) or retrospective studies that compared the effectiveness or safety of factor Xa inhibitors and enoxaparin in preventing thromboembolism in hospitalized patients with COVID-19. Embolic incidence, incidence of bleeding, and all-cause mortality were among the outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95 percent CIs. Results: The analysis included six RCTs and two retrospective studies containing 4048 patients. Meta-analysis showed a statistically significant reduction among patients on factor Xa inhibitors compared with low-molecular-weight heparin (LMWH) in the embolic incidence [risk ratio (RR) 0.64 (95%, CI 0.42, 0.98); P=0.04, I2=12%]. Upon subgroup analysis by type of study design, no significant reductions were noted in patients on factor Xa inhibitors in RCTs (RR: 0.62; 95% CI: 0.33-1.17; P=0.14) or observational studies (RR: 0.53; 95% CI: 0.23-1.26; P=0.15) when compared with enoxaparin Factor Xa inhibitors were not significantly associated with incidence of bleeding [RR 0.76 (95% CI 0.36, 1.61); P=0.47, I2=0%] or all-cause mortality (RR: 0.81; 95% CI: 0.48-1.36; P=0.43). Consistent results were obtained upon subgroup analysis by the type of study design. Conclusion: Factor Xa inhibitors are more effective than enoxaparin in preventing thromboembolism among patients with COVID-19 who are not acutely ill and are hospitalized. Additional rigorous RCTs comparing factor Xa inhibitors with enoxaparin are warranted.

Regional variations in antimicrobial susceptibility of community-acquired uropathogenic Escherichia coli in India: Findings of a multicentric study highlighting the importance of local antibiograms.

Objectives: Evidence-based prescribing is essential to optimize patient outcomes in cystitis. This requires knowledge of local antibiotic resistance rates. Diagnostic and Antimicrobial Stewardship (DASH) to Protect Antibiotics (https://dashuti.com/) is a multicentric mentorship program guiding centers in preparing, analyzing and disseminating local antibiograms to promote antimicrobial stewardship in community urinary tract infection. Here, we mapped the susceptibility profile of Escherichia coli from 22 Indian centers. Methods: These centers spanned 10 Indian states and three union territories. Antibiograms for urinary E. coli from the outpatient departments were collated. Standardization was achieved by regional online training; anomalies were resolved via consultation with study experts. Data were collated and analyzed. Results: Nationally, fosfomycin, with 94% susceptibility (inter-center range 83-97%), and nitrofurantoin, with 85% susceptibility (61-97%), retained the widest activity. The susceptibility rates were lower for co-trimoxazole (49%), fluoroquinolones (31%), and oral cephalosporins (26%). The rates for third- and fourth-generation cephalosporins were 46% and 52%, respectively, with 54% (33-58%) extended-spectrum ß-lactamase prevalence. Piperacillin-tazobactam (81%), amikacin (88%), and meropenem (88%) retained better activity; however, one center in Delhi recorded only 42% meropenem susceptibility. Susceptibility rates were mostly higher in South, West, and Northeast India; centers in the heavily populated Gangetic plains, across north and northwest India, had greater resistance. These findings highlight the importance of local antibiograms in guiding appropriate antimicrobial choices. Conclusions: Fosfomycin and nitrofurantoin are the preferred oral empirical choices for uncomplicated E. coli cystitis in India, although elevated resistance in some areas is concerning. Empiric use of fluoroquinolones and third-generation cephalosporins is discouraged, whereas piperacillin/tazobactam and aminoglycosides remain carbapenem-sparing parenteral agents.

Epigenetic regulation of tumor-immune symbiosis in glioma.

Glioma is a type of aggressive and incurable brain tumor. Patients with glioma are highly resistant to all types of therapies, including immunotherapies. Epigenetic reprogramming is a key molecular hallmark in tumors across cancer types, including glioma. Mounting evidence highlights a pivotal role of epigenetic regulation in shaping tumor biology and therapeutic responses through mechanisms involving both glioma cells and immune cells, as well as their symbiotic interactions in the tumor microenvironment (TME). In this review, we discuss the molecular mechanisms of epigenetic regulation that impacts glioma cell biology and tumor immunity in both a cell-autonomous and non-cell-autonomous manner. Moreover, we provide an overview of potential therapeutic approaches that can disrupt epigenetic-regulated tumor-immune symbiosis in the glioma TME.

Lactate dehydrogenase A regulates tumor-macrophage symbiosis to promote glioblastoma progression.

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase inhibitor stiripentol emerges as the top hit. Combined profiling and functional studies demonstrate that lactate dehydrogenase A (LDHA)-directed extracellular signal-regulated kinase (ERK) pathway activates yes-associated protein 1 (YAP1)/ signal transducer and activator of transcription 3 (STAT3) transcriptional co-activators in glioblastoma cells to upregulate C-C motif chemokine ligand 2 (CCL2) and CCL7, which recruit macrophages into the tumor microenvironment. Reciprocally, infiltrating macrophages produce LDHA-containing extracellular vesicles to promote glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis markedly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of tumor and plasma samples of glioblastoma patients confirms that LDHA and its downstream signals are potential biomarkers correlating positively with macrophage density. Thus, LDHA-mediated tumor-macrophage symbiosis provides therapeutic targets for glioblastoma.

Curcumin coating: a novel solution to mitigate inherent carbon nanotube toxicity.

Multi-walled Carbon Nanotubes (MWCNTs) are inert structures with high aspect ratios that are widely used as vehicles for targeted drug delivery in cancer and many other diseases. They are largely non-toxic in nature however, when cells are exposed to these nanotubes for prolonged durations or at high concentrations, they show certain adverse effects. These include cytotoxicity, inflammation, generation of oxidative stress, and genotoxicity among others. To combat such adverse effects, various moieties can be attached to the surface of these nanotubes. Curcumin is a known anti-inflammatory, antioxidant and cytoprotective compound derived from a medicinal plant called Curcuma longa. In this study, we have synthesized and characterized Curcumin coated-lysine functionalized MWCNTs and further evaluated the cytoprotective, anti-inflammatory, antioxidant and antiapoptotic effect of Curcumin coating on the surface of MWCNTs. The results show a significant decrease in the level of inflammatory molecules like IL-6, IL-8, IL-1ß, TNFα and NFκB in cells exposed to Curcumin-coated MWCNTs as compared to the uncoated ones at both transcript and protein levels. Further, compared to the uncoated samples, there is a reduction in ROS production and upregulation of antioxidant enzyme-Catalase in the cells treated with Curcumin-coated MWCNTs. Curcumin coating also helped in recovery of mitochondrial membrane potential in the cells exposed to MWCNTs. Lastly, cells exposed to Curcumin-coated MWCNTs showed reduced cell death as compared to the ones exposed to uncoated MWCNTs. Our findings suggest that coating of Curcumin on the surface of MWCNTs reduces its ability to cause inflammation, oxidative stress, and cell death.

Case report: A rare case of dual primary synchronous malignancies of the breast and kidney in a 70 year female.

INTRODUCTION: Multiple primary cancers (MPCs) have attracted attention in medical research due to their increasing incidence. The coexistence of invasive breast carcinoma and clear cell carcinoma of the kidney, alongside a family history of cancer, highlights the multifactorial origins of MPCs, particularly their potential association with genetic factors. CASE PRESENTATION: A 70-year-old female initially sought medical attention for a two-year history of a right breast lump as her primary concerns centered on the long-standing lump. Clinical evaluations and imaging studies revealed an invasive breast carcinoma diagnosis, and simultaneously, an incidental mass in her left kidney was identified as clear cell carcinoma. DISCUSSION: Emphasis and further researh should be on the potential role of genetic factors in MPC development, necessitating comprehensive genetic evaluations. CONCLUSION: This study highlights the significance of customized treatment approaches for each malignancy, facilitating early detection, improved patient outcomes, and an enhanced understanding of MPCs.

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications.

Information exchange is essential for the brain, where it communicates the physiological and pathological signals to the periphery and vice versa. Extracellular vesicles (EVs) are a heterogeneous group of membrane-bound cellular informants actively transferring informative calls to and from the brain via lipids, proteins, and nucleic acid cargos. In recent years, EVs have also been widely used to understand brain function, given their "cell-like" properties. On the one hand, the presence of neuron and astrocyte-derived EVs in biological fluids have been exploited as biomarkers to understand the mechanisms and progression of multiple neurological disorders; on the other, EVs have been used in designing targeted therapies due to their potential to cross the blood-brain-barrier (BBB). Despite the expanding literature on EVs in the context of central nervous system (CNS) physiology and related disorders, a comprehensive compilation of the existing knowledge still needs to be made available. In the current review, we provide a detailed insight into the multifaceted role of brain-derived extracellular vesicles (BDEVs) in the intricate regulation of brain physiology. Our focus extends to the significance of these EVs in a spectrum of disorders, including brain tumors, neurodegenerative conditions, neuropsychiatric diseases, autoimmune disorders, and others. Throughout the review, parallels are drawn for using EVs as biomarkers for various disorders, evaluating their utility in early detection and monitoring. Additionally, we discuss the promising prospects of utilizing EVs in targeted therapy while acknowledging the existing limitations and challenges associated with their applications in clinical scenarios. A foundational comprehension of the current state-of-the-art in EV research is essential for informing the design of future studies.

Imipridones inhibit tumor growth and improve survival in an orthotopic liver metastasis mouse model of human uveal melanoma.

Purpose: Uveal melanoma (UM) is a highly aggressive disease with very few treatment options. We previously demonstrated that mUM is characterized by high oxidative phosphorylation (OXPHOS). Here we tested the anti-tumor, signaling and metabolic effects of imipridones, CLPP activators which reduce OXPHOS indirectly and have demonstrated safety in patients. Experimental Design: We assessed CLPP expression in UM patient samples. We tested the effects of imipridones (ONC201, ONC212) on the growth, survival, signaling and metabolism of UM cell lines in vitro, and for therapeutic effects in vivo in UM liver metastasis models. Results: CLPP expression was confirmed in primary and mUM patient samples. ONC201/212 treatment of UM cell lines in vitro decreased OXPHOS effectors, inhibited cell growth and migration, and induced apoptosis. ONC212 increased metabolic stress and apoptotic pathways, inhibited amino acid metabolism, and induced cell death-related lipids. ONC212 also decreased tumor burden and increased survival in vivo in two UM liver metastasis models. Conclusion: Imipridones are a promising strategy for further testing and development in mUM.

Characterization of direct oral anticoagulants use in adult hematopoietic stem cell transplant recipients.

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) treatment are of interest in oncology due to ease of administration and lack of need for therapeutic monitoring compared to other anticoagulants. Data supporting their use in patients with hematologic malignancies post-hematopoietic stem cell transplant (HCT) are limited. The purpose of the study is to characterize DOAC use in HCT patients. This multicenter, retrospective cohort analysis included allogeneic and autologous HCT recipients. The primary outcome was major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB)/minor bleeding and VTE recurrence. Of 126 patients, 91 (72.2%) patients received an autologous HCT, and 35 (27.8%) patients received an allo-HCT. No major bleeding occurred in either transplant recipient groups. In autologous HCT recipients, CRNMB/minor bleeding occurred in four (4.4%) patients and VTE recurrence occurred in one (1.1%) patient. For allogeneic HCT recipients, CRNMB/minor bleeding occurred in five (14.3%) patients and VTE recurrence occurred in two (5.7%) patients. For patients that experienced a CRNMB, five (100%) of the allogeneic HCT and two (50%) of the autologous HCT recipients were thrombocytopenic at the time of bleeding. Only 38.5% of patients who experienced a drug-drug interaction requiring DOAC dose adjustment received the appropriate dose adjustment. DOACs were associated with low rates of recurrent VTE and no major bleeding events, similar to published data on DOAC use in the general cancer patient population. This suggests that DOACs may be safe therapeutic options with proactive management of drug interactions and careful monitoring for bleeding events, especially in the allogeneic HCT population where minor bleeding rates were slightly higher.

Needle-free electronically-controlled jet injector treatment with bleomycin and lidocaine is effective and well-tolerated in patients with recalcitrant keloids.

OBJECTIVES: The treatment of recalcitrant keloids is challenging. Although intralesional bleomycin using conventional needle injectors (CNI) is effective, it has important drawbacks, such as the need for repetitive and painful injections. Therefore, we aimed to evaluate the effectiveness, tolerability and patient satisfaction of intralesional bleomycin with lidocaine administered with a needle-free electronically-controlled pneumatic jet-injector (EPI) in recalcitrant keloids. METHODS: This retrospective study included patients with recalcitrant keloids who had received three intralesional EPI-assisted treatments with bleomycin and lidocaine. Effectiveness was assessed using the Patient and Observer Scar Assessment Scale (POSAS) at baseline and four to six weeks after the third treatment. Additionally, treatment related pain scores numeric rating scale, adverse effects, patient satisfaction and Global Aesthetic Improvement Scale (GAIS) were assessed. RESULTS: Fifteen patients with a total of >148 recalcitrant keloids were included. The median total POSAS physician- and patient-scores were respectively 40 and 41 at baseline, and reduced with respectively 7 and 6-points at follow-up ( p < 0.001; p < 0.001). The median pain scores during EPI-assisted injections were significantly lower compared to CNI-assistant injections, (2.5 vs. 7.0, respectively ( p < 0.001)). Adverse effects were mild. Overall, patients were "satisfied" or "very satisfied" with the treatments (14/15, 93.3%). The GAIS was "very improved" in one patient, "improved" in nine patients and "unaltered" in four patients. CONCLUSIONS: EPI-assisted treatment with bleomycin and lidocaine is an effective, well tolerated, patient-friendly alternative for CNI in patients with recalcitrant keloid scars. Randomized controlled trials are warranted to confirm our findings and improve the clinical management of recalcitrant keloids.

Trends and advances in pre- and post-harvest processing of linseed oil for quality food and health products.

Linseed is an ancient crop used for diverse purposes since the beginning of civilization. In recent times, linseed has emerged as a superfood due to its high content of health-promoting omega-3 fatty acids and other bioactive compounds. Among primary health effects, it has potential to manage hypertension, diabetes, osteoporosis, atherosclerosis, cancer, arthritis, neurological, cardiovascular diseases including blood cholesterol levels, constipation, diarrhea, and autoimmune disorders etc. due to the presence of omega-3 fatty acid, lignans, high dietary fibers, and proteins, whereas, secondary health effects comprise of relieving from various skin disorders. Due to these health-beneficial properties, interest in linseed oil necessitates the intensification of research efforts on various aspects. These include cultivation technology, varietal and genetic improvement, post-harvest processing, profiling of nutrients and bioactive compounds, pre-clinical and clinical studies, etc. The present review discussed the advances in linseed research including pre- and post-harvest processing. However, focus on the bioactive compounds present in linseed oil and their health effects are also presented. Linseed cultivation, pre- and post-harvest processing aspects are covered including climatic, edaphic, agronomic factors, type of cultivar and storage conditions etc, which impact the overall oil yield and its nutritional quality. Various emerging applications of linseed oil in functional food, nutraceutical, pharmaceutical, and cosmeceutical preparations were also presented in detail. Further, recommendations were made on linseed oil research in the field of genetics, breeding germplasm resources and genome editing for exploring its full applications as a nutrition and health product.

Hypoxia-driven protease legumain promotes immunosuppression in glioblastoma.

Glioblastoma (GBM) is a hypoxic and "immune-cold" tumor containing rich stromal signaling molecules and cell populations, such as proteases and immunosuppressive tumor-associated macrophages (TAMs). Here, we seek to profile and characterize the potential proteases that may contribute to GBM immunosuppression. Legumain (LGMN) emerges as the key protease that is highly enriched in TAMs and transcriptionally upregulated by hypoxia-inducible factor 1-alpha (HIF1α). Functionally, the increased LGMN promotes TAM immunosuppressive polarization via activating the GSK-3ß-STAT3 signaling pathway. Inhibition of macrophage HIF1α and LGMN reduces TAM immunosuppressive polarization, impairs tumor progression, enhances CD8+ T cell-mediated anti-tumor immunity, and synergizes with anti-PD1 therapy in GBM mouse models. Thus, LGMN is a key molecular switch connecting two GBM hallmarks of hypoxia and immunosuppression, providing an actionable therapeutic intervention for this deadly disease.

LDHA-regulated tumor-macrophage symbiosis promotes glioblastoma progression.

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase (LDH) inhibitor stiripentol (an FDA-approved anti-seizure drug for Dravet Syndrome) emerges as the top hit. Combined profiling and functional studies demonstrate that LDHA-directed ERK pathway activates YAP1/STAT3 transcriptional co-activators in glioblastoma cells to upregulate CCL2 and CCL7, which recruit macrophages into the tumor microenvironment. Reciprocally, infiltrating macrophages produce LDHA-containing extracellular vesicles to promote glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis markedly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of tumor and plasma samples of glioblastoma patients confirms that LDHA and its downstream signals are potential biomarkers correlating positively with macrophage density. Thus, LDHA-mediated tumor-macrophage symbiosis provides therapeutic targets for glioblastoma.

Kunitz-type protease inhibitor TFPI2 remodels stemness and immunosuppressive tumor microenvironment in glioblastoma.

Glioblastoma (GBM) tumors consist of multiple cell populations, including self-renewing glioblastoma stem cells (GSCs) and immunosuppressive microglia. Here we identified Kunitz-type protease inhibitor TFPI2 as a critical factor connecting these cell populations and their associated GBM hallmarks of stemness and immunosuppression. TFPI2 promotes GSC self-renewal and tumor growth via activation of the c-Jun N-terminal kinase-signal transducer and activator of transcription (STAT)3 pathway. Secreted TFPI2 interacts with its functional receptor CD51 on microglia to trigger the infiltration and immunosuppressive polarization of microglia through activation of STAT6 signaling. Inhibition of the TFPI2-CD51-STAT6 signaling axis activates T cells and synergizes with anti-PD1 therapy in GBM mouse models. In human GBM, TFPI2 correlates positively with stemness, microglia abundance, immunosuppression and poor prognosis. Our study identifies a function for TFPI2 and supports therapeutic targeting of TFPI2 as an effective strategy for GBM.

BRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast cancer.

Background & objectives: Studies have shown that apart from hereditary breast carcinomas, breast cancer susceptibility gene 1 (BRCA1) mutations conferring to its loss are seen in sporadic breast carcinomas (SBC) as well. The aim of the present study was to assess BRCA1 methylation in females presenting at King George's Medical University, Lucknow, with SBC by both immunohistochemistry (IHC) and methylation PCR with respect to hormonal profile and various morphological prognostic parameters. The primary objective was to look for the association between BRCA1 protein expression and DNA promoter methylation. Methods: 81 mastectomy specimens from SBC of invasive breast carcinoma (no special type) were included in this study. After a detailed morphological assessment, formalin fixed paraffin embedded tissue from a representative tumour area was selected for BRCA1 IHC by heat-mediated antigen retrieval under high pH and DNA extraction and further bisulphate treatment. BRCA1 was studied for methylation by methylated and unmethylated PCR-specific primers. Results: BRCA1 promoter methylation was present in 42/81 (51.9%) participants, with significant BRCA1 protein loss (72.7%; P=0.002). A significant association between BRCA1 loss and hormonal profile was found (P=0.001); maximum in triple negative breast carcinoma (TNBC) (72%; 18/25). Most of the TNBC also harboured methylation (68%). Although not significant grade II and III tumours, lymph vascular invasion, ductal carcinoma in situ, and nodal metastasis (≥3) were seen in a higher percentage in methylated tumours. Mortality in SBC was significantly associated with BRCA1 loss (30.3%; P=0.024). Interpretation & conclusions: Study results highlight the concept of "BRCAness" in SBC as well. Hence, we can confer that identification of BRCA1 loss in SBC can make it a perfect candidate for poly ADP-ribose polymerase inhibitors or cisplatin-based therapy like hereditary ones.

Light-Driven Catalytic Activity of Green-Synthesized SnO2/WO3-x Hetero-nanostructures.

This work reports an environmentally friendly and economically feasible green synthesis of monometallic oxides (SnO2 and WO3) and their corresponding mixed metal oxide (SnO2/WO3-x) nanostructures from the aqueous Psidium guajava leaf extract for light-driven catalytic degradation of a major industrial contaminant, methylene blue (MB). P. guajava is a rich source of polyphenols that acts as a bio-reductant as well as a capping agent in the synthesis of nanostructures. The chemical composition and redox behavior of the green extract were investigated by liquid chromatography-mass spectrometry and cyclic voltammetry, respectively. Results acquired by X-ray diffraction and Fourier transform infrared spectroscopy confirm the successful formation of crystalline monometallic oxides (SnO2 and WO3) and bimetallic SnO2/WO3-x hetero-nanostructures capped with polyphenols. The structural and morphological aspects of the synthesized nanostructures were analyzed by transmission electron microscopy and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. Photocatalytic activity of the synthesized monometallic and hetero-nanostructures was investigated for the degradation of MB dye under UV light irradiation. Results indicate a higher photocatalytic degradation efficiency for mixed metal oxide nanostructures (93.5%) as compared to pristine monometallic oxides SnO2 (35.7%) and WO3 (74.5%). The hetero-metal oxide nanostructures prove to be better photocatalysts with reusability up to 3 cycles without any loss in degradation efficiency or stability. The enhanced photocatalytic efficiency is attributed to a synergistic effect in the hetero-nanostructures, efficient charge transportation, extended light absorption, and increased adsorption of dye due to the enlarged specific surface area.

Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states.

Glioblastoma (GBM) diffusely infiltrates the brain and intermingles with non-neoplastic brain cells, including astrocytes, neurons and microglia/myeloid cells. This complex mixture of cell types forms the biological context for therapeutic response and tumor recurrence. We used single-nucleus RNA sequencing and spatial transcriptomics to determine the cellular composition and transcriptional states in primary and recurrent glioma and identified three compositional 'tissue-states' defined by cohabitation patterns between specific subpopulations of neoplastic and non-neoplastic brain cells. These tissue-states correlated with radiographic, histopathologic, and prognostic features and were enriched in distinct metabolic pathways. Fatty acid biosynthesis was enriched in the tissue-state defined by the cohabitation of astrocyte-like/mesenchymal glioma cells, reactive astrocytes, and macrophages, and was associated with recurrent GBM and shorter survival. Treating acute slices of GBM with a fatty acid synthesis inhibitor depleted the transcriptional signature of this pernicious tissue-state. These findings point to therapies that target interdependencies in the GBM microenvironment.

Tumor microenvironment signaling and therapeutics in cancer progression.

Tumor development and metastasis are facilitated by the complex interactions between cancer cells and their microenvironment, which comprises stromal cells and extracellular matrix (ECM) components, among other factors. Stromal cells can adopt new phenotypes to promote tumor cell invasion. A deep understanding of the signaling pathways involved in cell-to-cell and cell-to-ECM interactions is needed to design effective intervention strategies that might interrupt these interactions. In this review, we describe the tumor microenvironment (TME) components and associated therapeutics. We discuss the clinical advances in the prevalent and newly discovered signaling pathways in the TME, the immune checkpoints and immunosuppressive chemokines, and currently used inhibitors targeting these pathways. These include both intrinsic and non-autonomous tumor cell signaling pathways in the TME: protein kinase C (PKC) signaling, Notch, and transforming growth factor (TGF-ß) signaling, Endoplasmic Reticulum (ER) stress response, lactate signaling, Metabolic reprogramming, cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) and Siglec signaling pathways. We also discuss the recent advances in Programmed Cell Death Protein 1 (PD-1), Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), T-cell immunoglobulin mucin-3 (TIM-3) and Lymphocyte Activating Gene 3 (LAG3) immune checkpoint inhibitors along with the C-C chemokine receptor 4 (CCR4)- C-C class chemokines 22 (CCL22)/ and 17 (CCL17), C-C chemokine receptor type 2 (CCR2)- chemokine (C-C motif) ligand 2 (CCL2), C-C chemokine receptor type 5 (CCR5)- chemokine (C-C motif) ligand 3 (CCL3) chemokine signaling axis in the TME. In addition, this review provides a holistic understanding of the TME as we discuss the three-dimensional and microfluidic models of the TME, which are believed to recapitulate the original characteristics of the patient tumor and hence may be used as a platform to study new mechanisms and screen for various anti-cancer therapies. We further discuss the systemic influences of gut microbiota in TME reprogramming and treatment response. Overall, this review provides a comprehensive analysis of the diverse and most critical signaling pathways in the TME, highlighting the associated newest and critical preclinical and clinical studies along with their underlying biology. We highlight the importance of the most recent technologies of microfluidics and lab-on-chip models for TME research and also present an overview of extrinsic factors, such as the inhabitant human microbiome, which have the potential to modulate TME biology and drug responses.

Decreasing the Rate of Surgical Site Infection in Patients Operated by Cesarean Section in a Tertiary Care Hospital in India: A Quality Improvement Initiative.

Background Surgical site infections (SSIs) are a substantial cause of maternal morbidity and are associated with a significant increase in hospital stay and cost. The prevention of SSI is complex and requires the integration of a range of measures before, during, and after surgery. Jawaharlal Nehru Medical College (JNMC), Aligarh Muslim University (AMU) is one of the referral centers of India with a huge influx of patients. Methods The project was undertaken by the Department of Obstetrics and Gynaecology, JNMC, AMU, Aligarh. Our department was sensitized to the need for quality improvement (QI) through Laqshya, a Government of India initiative for labor rooms in 2018. We were facing problems like a high surgical site infection rate, poor documentation and records, no standard protocols, overcrowding, and no admission discharge policy. There was a high rate of surgical site infections, leading to maternal morbidity, increased days of hospitalization, more usage of antibiotics, and increased financial burden. A multidisciplinary quality improvement (QI) team was formed comprising obstetricians and gynecologists, the hospital infection control team, the head of the neonatology unit, staff nurses, and multitasking staff (MTS) workers. Results The baseline data were collected for a period of one month and it was found that the rate of SSI was around 30%. Our aim was to decrease the rate of SSI from 30% to less than 5% over a period of six months. The QI team worked meticulously, implemented evidence-based measures, regularly analyzed the results, and devised measures to overcome the obstacles. The point-of-care improvement (POCQI) model was adopted for the project. The rate of SSI decreased significantly in our patients and the rates are around 5% persistently. Conclusion The project not only helped in decreasing the infection rates but also led to vast improvements in the department with the formulation of an antibiotic policy, surgical safety checklist, and admission-discharge policy.