Role of bio-flavonols and their derivatives in improving mitochondrial dysfunctions associated with pancreatic tumorigenesis.

Mitochondria, a cellular metabolic center, efficiently fulfill cellular energy needs and regulate crucial metabolic processes, including cellular proliferation, differentiation, apoptosis, and generation of reactive oxygen species. Alteration in the mitochondrial functions leads to metabolic imbalances and altered extracellular matrix dynamics in the host, utilized by solid tumors like pancreatic cancer (PC) to get energy benefits for fast-growing cancer cells. PC is highly heterogeneous and remains unidentified for a longer time because of its complex pathophysiology, retroperitoneal position, and lack of efficient diagnostic approaches, which is the foremost reason for accounting for the seventh leading cause of cancer-related deaths worldwide. PC cells often respond poorly to current therapeutics because of dense stromal barriers in the pancreatic tumor microenvironment, which limit the drug delivery and distribution of antitumor immune cell populations. As an alternative approach, various natural compounds like flavonoids are reported to possess potent antioxidant and anticancerous properties and are less toxic than current chemotherapeutic drugs. Therefore, we aim to summarize the current state of knowledge regarding the pharmacological properties of flavonols in PC in this review from the perspective of mitigating mitochondrial dysfunctions associated with cancer cells. Our literature survey indicates that flavonols efficiently regulate cellular metabolism by scavenging reactive oxygen species, mitigating inflammation, and arresting the cell cycle to promote apoptosis in tumor cells via intrinsic mitochondrial pathways. In particular, flavonols proficiently inhibit the cancer-associated proliferation and inflammatory pathways such as EGFR/MAPK, PI3K/Akt, and nuclear factor κB in PC. Overall, this review provides in-depth evidence about the therapeutic potential of flavonols for future anticancer strategies against PC; still, more multidisciplinary human interventional studies are required to dissect their pharmacological effect accurately.

Electrochemical behavior, antimicrobial activities, and effect of temperature on micellization of imidazolium monomeric surfactants.

In the present study, we herein report the conductance behavior, effect of temperature, and chain-length of two environmentally friendly imidazolium cationic capric and stearic surfactants. The conductance behavior has been carried out in aqueous solvent (H2O) at four different temperatures such as 24 °C, 29 °C, 34 °C, and 39 °C. The normal micelles were formed in an aqueous solvent and critical micelle concentration (CMC) can be estimated through conductivity parameters. The expected dependency of the CMC on the alkyl chain length of the 3-(2-(decanoyloxy)ethyl)-1-methyl-1H-imidazol-3-ium-bromide and 3-(2-(octadecanoyloxy)ethyl)-1-methyl-1H-imidazol-3-ium-bromide was demonstrated. It was observed that the graphs of molar conduct activity v/s square root were not linear, which specifies that the synthesized surfactants behave as weak electrolytes in the dilute solutions. The electrochemical characterization of capric and stearic surfactant modified SPCE was studied in 1mM K3FeCN6 solution. The CS/SPCE and SS/SPCE were shown elevated sensitivity, high stability, and excellent conductivity. Moreover, the antimicrobial behaviors of the synthesized imidazolium cationic surfactants versus various microbial strains were evaluated. Results showed that capric surfactant demonstrated high antibacterial activity against Escherichia coli (MIC > 31.5 µg/mL).

Development of metal free carbon catalyst derived from Parthenium hysterophorus for the electrochemical detection of dopamine.

Parthenium hysterophorus, one of the seven most hazardous weeds is widely known for its allergic, respiratory and skin-related disorders. It is also known to affect biodiversity and ecology. For eradication of the weed, its effective utilization for the successful synthesis of carbon-based nanomaterial is a potent management strategy. In this study, reduced graphene oxide (rGO) was synthesized from weed leaf extract through a hydrothermal-assisted carbonization method. The crystallinity and geometry of the as-synthesized nanostructure are confirmed from the X-ray diffraction study, while the chemical architecture of the nanomaterial is ascertained through X-ray photoelectron spectroscopy. The stacking of flat graphene-like layers with a size range of ∼200-300 nm is visualized through high-resolution transmission electron microscopy images. Further, the as-synthesized carbon nanomaterial is advanced as an effective and highly sensitive electrochemical biosensor for dopamine, a vital neurotransmitter of the human brain. Nanomaterial oxidizes dopamine at a much lower potential (0.13 V) than other metal-based nanocomposites. Moreover, the obtained sensitivity (13.75 and 3.31 µA µM-1 cm-2), detection limit (0.6 and 0.8 µM), the limit of quantification (2.2 and 2.7 µM) and reproducibility calculated through cyclic voltammetry/differential pulse voltammetry respectively outcompete many metal-based nanocomposites that were previously used for the sensing of dopamine. This study boosts the research on the metal-free carbon-based nanomaterial derived from waste plant biomass.

Is Chemical Cauterization Safe on Septal Cartilage in Treatment of Recurrent Epistaxis?

Epistaxis is one of the most common emergencies. Topical agents such as silver nitrate, is known to be a strong oxidizing agent and have been widely used, especially in recurrent and refractory cases. The extent of depth of coagulative necrosis is dependent on time of exposure and concentration. 2 mm wide bar of nasal septum from 30 patients was taken and AgNO3 was applied for 10, 20, 40 s. H&E staining was then performed to see depth of penetration and intensity of stain deposits. It was observed that with increase time of application, depth of penetration and density of deposits were increased for both 75% and 100% concentration of solution. Distribution in depth of penetration was significant when 75% concentration was applied for more than 20 s. But when 100% concentration was used, similar findings were found even after 10 s in young age group. Our study shows that when silver nitrate is used for chemical cauterization in different concentrations and for different times, their penetration is different. Moreover, the depth of penetration depends more on the time of contact than concentration of silver nitrate. We would recommend using 75% solution for use with a contact time not more than 20 s in adults and 10 s in children.

Electron-Beam Induced Emergence of Mesoscopic Ordering in Layered MnPS3.

Ordered mesoscale structures in 2D materials induced by small misorientations have allowed for a wide variety of electronic, ferroelectric, and quantum phenomena to be explored. Until now, the only mechanism to induce this periodic ordering was via mechanical rotations between the layers, with the periodicity of the resulting moiré pattern being directly related to twist angle. Here we report a fundamentally distinct mechanism for emergence of mesoscopic periodic patterns in multilayer sulfur-containing metal phosphorus trichalcogenide, MnPS3, induced by the electron beam. The formation under the beam of periodic hexagonal patterns with several characteristic length scales, nucleation and transitions between the phases, and local dynamics are demonstrated. The associated mechanisms are attributed to the relative contraction of the layers caused by beam-induced sulfur vacancy formation with subsequent ordering and lattice parameter change. As a result, the plasmonic response of the system is locally altered, suggesting an element of control over plasmon resonances by electron beam patterning. We pose that harnessing this phenomenon provides both insight into fundamental physics of quantum materials and enables device applications by enabling controlled periodic potentials on the atomic scale.

CCR4+ monocytic myeloid-derived suppressor cells are associated with the increased epithelial-mesenchymal transition in pancreatic adenocarcinoma patients.

Among all the cancer-related deaths globally, pancreatic ductal adenocarcinoma (PDAC) accounts for the seventh leading cause of mortality. A dysregulated immune system disrupts anti-tumor immunity by abnormal accumulation of myeloid-derived suppressor cells (MDSCs), but the underlying mechanisms are still inconclusive. To gain new insights into the role of MDSCs in tumor settings, we aimed to determine the mechanism of expansion of various subsets of MDSCs in PDAC patients and their role in promoting invasiveness. We assessed the load of MDSCs, chemokines responsible for the recruitment of MDSCs in PDAC patients by flow cytometry. We investigated the chemokine profile of tumor tissue using qRT-PCR and the status of epithelial-mesenchymal transition (EMT) related markers E-Cadherin, N-Cadherin, Snail, and ZEB1 by qRT-PCR and immunohistochemistry. We found a higher frequency of tumor infiltrated MDSCs in PDAC patients. Chemokine ligands CCL2 and the receptor CCR4 were markedly elevated in the PDAC tumor, while CCR4+ monocytic MDSCs (M-MDSCs) were found significantly elevated in peripheral blood and tumor tissue. In tumor tissue, expression of E-Cadherin was significantly reduced, while N-Cadherin, Snail, and ZEB1 were markedly raised. The frequency of CCR4+ M-MDSCs significantly correlated with the expression of mesenchymal transition markers N-Cadherin, Snail, and ZEB1. Collectively, these results suggest that the CCL2-CCR4 axis plays a crucial role in driving the recruitment of M-MDSCs, which is associated with increased invasiveness in PDAC. This study sheds light on the expansion mechanism of MDSCs, which can serve as a crucial target of future anti-cancer strategies to inhibit tumor cell invasiveness.

Senescent chondrogenic progenitor cells derived from articular cartilage of knee osteoarthritis patients contributes to senescence-associated secretory phenotype via release of IL-6 and IL-8.

OBJECTIVES: Despite the presence of chondrogenic progenitor cells (CPCs) in knee osteoarthritis patients they are unable to repair the damaged cartilage. This study aimed to evaluate the oxidative stress, cellular senescence, and senescence-associated secretory phenotype (SASP) in the CPCs derived from osteoarthritic cartilage and compare with the CPCs of healthy articular cartilage. METHODS: Isolated CPCs were characterized based on phenotypic expression of stem cell markers, clonogenicity, and tri-lineage differentiation assay. Production of ROS was measured using DCFDA assay. Cellular senescence in CPCs was assessed by senescence-associated beta-galactosidase assay and expression of senescence markers at the gene level using real-time PCR. Morphological features associated with senescent OA-CPCs were studied using scanning electron microscopy. To study SASP, the production of inflammatory cytokines was assessed in the culture supernatant using a flow-cytometer based cytometric bead array. RESULTS: OA-CPCs exhibited elevated ROS levels along with a relatively high percentage of senescent cells compared to non-OA CPCs, and a positive correlation exists between ROS production and senescence. The morphological assessment of senescent CPCs revealed increased cell size and multiple nuclei in senescent OA-CPCs. These results were further validated by elevated expression of senescence genes p16, p21, and p53. Additionally, culture supernatant of senescent OA-CPCs expressed IL-6 and IL-8 cytokines indicative of SASP. CONCLUSIONS: Despite exhibiting similar expression of stem cell markers and clonogenicity, CPCs undergo oxidative stress in diseased knee joint leading to increased production of intracellular ROS in chondrogenic progenitor cells that support cellular senescence. Further, senescence in OA-CPCs is mediated via the release of pro-inflammatory cytokines, IL-6 and IL-8.

Styloid Process; Correlation Between Symptoms, Palpability and Measurements on Three Dimensional Computed Tomography.

Styloid process is a long and slender osseous projection protruding downward, forward and slightly medially from the temporal bone and serves as an anchor point for various muscles associated with the tongue and the larynx. The aim of the present study was to record the length and the angle of Styloid process on three dimensional computed tomography in patients with unilateral symptomatic and palpable styloid process and compare the length and the angle of styloid process of symptomatic side to asymptomatic side on three dimensional computed tomography. 3D-CT face reconstruction were perfomed in all 35 patients (17 females, 18 males of age range 25-69 years). The length of the styloid process and its angulation (transverse and sagittal angles) were measured by means of three dimensional and multiplanar reconstruction images. The length of styloid process on symptomatic side had a mean of 33.61 ± 5.08 mm while on asymptomatic side mean was 31.11 ± 5.02 mm. The mean transverse angle on symptomatic sides had a mean of 72.37° ± 4.48° while on asymptomatic side mean was 74.17° ± 4.48°. The mean sagittal angle seen on symptomatic side was 88.11° ± 5.21° while on asymptomatic side was 87.88° ± 5.03°. Symptomatic side has a longer styloid. Length of the styloid process has a statistical correlation with the symptoms and symptomatic side has a longer styloid. Though there was a difference in transverse and sagittal angulation in symptomatic versus asymptomatic side; but it was not statistically significant. On examination of the opposite asymptomatic side, 5 patients had a palpable styloid process therefore we infer that long styloid process may not always be associated with symptoms. Patients with cervicofacial pain should be evaluated for Eagle syndrome by palpation of styloid process in the tonsillar fossa and further by three dimensional computed tomography (3D-CT). 3D CT is an effective tool in evaluating patients with cervicofacial pain and making a diagnosis of Eagle's syndrome. Therefore, 3D CT should be performed while evaluating patients with these symptoms.

Presentations of Pediatric Emergencies in a Tertiary Teaching Hospital in North India: An Overview.

Pediatric otorhinolaryngological emergencies constitute a major portion in emergency room presentations. The etiology of ENT problems in children is different from those in adults. Most of these can be managed conservatively while some need prompt management at a well equipped centre. To analyze the etiology, clinical profile and line of management of pediatric otorhinolaryngological emergencies. Retrospectively, records of 452 children up to the age of 16 years presenting with ENT complaints were included in the study. Out of 452 patients, 148 presented with aural complaints, 129 had nasal problems and 175 patients with throat complaints. They were classified into Trauma 69 (15.26%), Foreign body 278 (61.50%), Infective 82 (08.14%) and allergic/miscellaneous 23 (05.10%) cases. In aural complaints, foreign body insertion seen in 57 (12.17%) cases while earache in 55 (12.15%) patients. In patients with nasal complaints, foreign body was present in 78 (17.26%) cases. Nasal bleeding and discharge or pain and swelling around nose were the other presentations. Respiratory distress was present in 66 (14.60%) patients while 74 (16.37%) patients came with ingestion of some foreign body. Neck swellings were seen in 20 (04.42%) patients and 15 (03.31%) patients came with history of rashes, feeling of choking or allergic reactions. Surgical intervention after admission was the top most intervention in 202 (44.69%) patients followed by conservative management in 110 (24.33%) patients who were treated and then sent home from emergency centre itself. Minor surgical intervention was sufficient to treat 78 (17.25%) patients without admission. Most common ENT emergency was foreign bodies and these cases need operative intervention. Specialist ENT personnel is needed to handle these cases. Parents must be educated to keep likely causes of these foreign bodies out of reach of growing children and also need to be educated about signs like severe pain, dyspnoea, bleeding or unilateral nasal discharge for timely management.

Oxygen Vacancy Injection as a Pathway to Enhancing Electromechanical Response in Ferroelectrics.

Since their discovery in late 1940s, perovskite ferroelectric materials have become one of the central objects of condensed matter physics and materials science due to the broad spectrum of functional behaviors they exhibit, including electro-optical phenomena and strong electromechanical coupling. In such disordered materials, the static properties of defects such as oxygen vacancies are well explored but the dynamic effects are less understood. In this work, the first observation of enhanced electromechanical response in BaTiO3 thin films is reported driven via dynamic local oxygen vacancy control in piezoresponse force microscopy (PFM). A persistence in peizoelectricity past the bulk Curie temperature and an enhanced electromechanical response due to a created internal electric field that further enhances the intrinsic electrostriction are explicitly demonstrated. The findings are supported by a series of temperature dependent band excitation PFM in ultrahigh vacuum and a combination of modeling techniques including finite element modeling, reactive force field, and density functional theory. This study shows the pivotal role that dynamics of vacancies in complex oxides can play in determining functional properties and thus provides a new route toward- achieving enhanced ferroic response with higher functional temperature windows in ferroelectrics and other ferroic materials.

Applications of the High Impact Practices in Family Planning during COVID-19.

The COVID-19 pandemic has substantially strained health systems across the globe. In particular, documented disruptions to voluntary family planning and reproductive health care due to competing health priorities, service disruptions, stockouts, and lockdowns are significantly impacting reproductive, maternal, newborn, and child health. As governments and family planning programmes grapple with how best to respond to the direct and indirect effects of the pandemic on family planning and reproductive health (FP/RH), the implementation and adaptation of evidence-based practices is crucial. In this commentary, we outline applications of the High Impact Practices in Family Planning (HIPs) towards COVID-19 response efforts. The HIPs are a set of evidence-based family planning practices which reflect global expert consensus on what works in family planning programming. Drawing upon preliminary COVID-19 data, documented experiences from prior health emergencies, and recommended programme adaptations from a variety of global health partners, we outline situations where specific HIPs may assist family planning programme managers in developing context-specific and evidence-based responses to COVID-19-related impacts on FP/RH, with the ultimate goal of ensuring the accessibility, availability, and continuity of voluntary family planning services across the world.

Exotic Long-Range Surface Reconstruction on La0.7Sr0.3MnO3 Thin Films.

Due to an extremely diverse phase space, La1-xSrxMnO3, as with other manganites, offers a wide range of tunability and applications including colossal magnetoresistance and use as spin-polarized electrodes. Here, we study an unprecedented, exotic surface reconstruction (6 × 6) in La1-xSrxMnO3 (x = 0.3) observed via low-energy electron diffraction (LEED). Scanning tunneling microscopy (STM) shows the surface is relatively flat, with unit-cell step heights, and X-ray photoelectron spectroscopy (XPS) reveals a strong degree of Sr segregation at the surface. By combining electron diffraction and first-principles computations, we propose that the long-range surface reconstruction consists of a Sr-segregated surface with La (6 × 6) ordering. This study expands our understanding of manganite systems and underscores their ability to form interesting surface reconstructions, driven largely by cation segregation that can potentially be controlled for tuning surface ordering.

Myeloid-derived suppressor cells: Bridging the gap between inflammation and pancreatic adenocarcinoma.

Pancreatic cancer has been identified as one of the deadliest malignancies because it remains asymptomatic and usually presents in the advanced stage. Tumour immune evasion is a well-known mechanism of tumorigenesis in various forms of human malignancies. Chronic inflammation via complex networking of various inflammatory cytokines in the local tissue microenvironment dysregulates the immune system and support tumour development. Pro-inflammatory mediators present in the tumour microenvironment increase the tumour burden by causing immune suppression through the generation of myeloid-derived suppressor cells (MDSCs) and T regulatory cells. These cells, along-with myofibroblasts, create a highly immunosuppressive and resistant tumour microenvironment and are thus considered as one of the culprits for the failure of anti-cancer chemotherapies in pancreatic adenocarcinoma patients. Targeting these MDSCs using various combinatorial approaches might have the potential for abrogating the resistance and suppressive nature of the pancreatic tumour microenvironment. Therefore, there is more curiosity in studying the crosstalk of MDSCs with other immune cells during pathological conditions and the underlying mechanisms of immunosuppression in the current scenario. In this article, the possible role of MDSCs in inflammation-mediated tumour progression of pancreatic adenocarcinoma has been discussed.

IL-6 is associated with expansion of myeloid-derived suppressor cells and enhanced immunosuppression in pancreatic adenocarcinoma patients.

Chronic inflammation favours the expansion of myeloid-derived suppressor cells (MDSCs) by secreting pro-inflammatory mediators. The role of MDSCs in mediating immunosuppression in pancreatic adenocarcinoma and in defining a premalignant route from chronic pancreatitis remains unclear. We aimed to study the immunosuppressive potential of all subsets of MDSCs and their correlation with inflammatory cytokines in pancreatic adenocarcinoma and chronic pancreatitis. Relative frequencies of MDSCs, immunosuppressive markers arginase-1 (ARG-1), programmed death-ligand 1 (PD-L1), reactive oxygen species (ROS) and cytokines in circulation and surgically resected local pancreatic tissue of chronic pancreatitis and pancreatic adenocarcinoma patients were analysed by multicolour flow cytometry and cytokine bead array, respectively. Levels of cytokines involved in MDSCs activation were analysed by ELISA, and the immunosuppressive nature of MDSCs was confirmed by T-cell suppression assay. Frequencies of circulating MDSCs and ARG-1, PD-L1, and ROS were significantly higher in pancreatic adenocarcinoma than healthy controls and showed a significant positive correlation with MDSCs burden in cancer tissue. Serum levels of cytokines IL-6, IL-8 and IL-10 were significantly elevated in pancreatic adenocarcinoma. IL-6 serum levels showed a significant positive correlation with frequencies of circulating MDSCs in pancreatic adenocarcinoma patients, and MDSCs mediated suppression of T-cell proliferation in vitro was associated with elevated IL-6 levels in the cell culture medium. Collectively, our results suggest that IL-6 plays a crucial role in the expansion of MDSCs and activating their immunosuppressive nature in pancreatic adenocarcinoma. The relative frequency of MDSCs in circulation can be used as a potential diagnostic biomarker for pancreatic cancer.

Intraoperative tragal and conchal cartilage thickness: Comparative study for cartilage tympanoplasty.

INTRODUCTION: In conditions like recurrent perforations, atelectatic tympanic membrane and poor eustachian tube function, temporalis fascia graft fails to give the desired result. In such cases cartilage is used for tympanoplasty. It was demonstrated that if the thickness of cartilage is reduced to around 0.5 mm, the sound conduction is comparable to that of normal tympanic membrane with excellent mechanical stability. AIM: To intra-operatively measure the mean thickness of tragal and conchal cartilage and compare it for age and sex variations. MATERIAL & METHODS: A total of 114 tragal and conchal cartilage samples of 86 patients were included in the study. Thickness of cartilages was measured intra-operatively after removing the perichondrium from both sides. RESULTS: Out of 58 tragal cartilages, 32 were from males and 26 from females. Mean thickness was 1.18 ± 0.11 mm among males and 1.12 ± 0.14 mm among females. Out of 56 conchal cartilage taken, 29 were from males and 27 females. Mean thickness among males were 1.38 ± 0.13 mm and 1.35 ± 0.08 mm in females. In 28 patients both tragal and conchal cartilage was taken. Mean thickness of both tragal (1.22 mm) and conchal cartilage (1.36 mm) increased with increase in age. Among 16 males in whom both cartilages were taken, mean thickness of tragal cartilage was 1.25 ± 0.11 mm and conchal cartilage was 1.41 ± 0.12 mm. Similarly among 12 females where both cartilages were taken, mean thickness of tragal cartilage was 1.20 ± 0.13 mm and conchal cartilage was 1.35 ± 0.07 mm. CONCLUSION: Sliced cartilage tympanoplasty is a relatively better technique. When using cartilage splitter to get sliced cartilage, ideally thickness of every graft should be known. As it is difficult to measure the exact thickness in every case, so knowing the mean for age and sex for cartilage thickness is important to have an idea of which plates to use for a successful outcome of slicing. We concluded that thickness of tragal cartilage is significantly less than the thickness of conchal cartilage. Also there is significant age related difference between mean thickness of cartilages, both for tragal and conchal cartilage. Surprisingly the difference between thickness in male and female is not statistically different.

Chemical composition, and antibacterial and antioxidant activities of essential oils from Laggera tomentosa Sch. Bip. ex Oliv. et Hiern (Asteraceae).

Laggera tomentosa Sch. Bip. ex Oliv. et Hiern (Asteraceae), an endemic Ethiopian medicinal plant, is traditionally used to treat various ailments. Previously, the chemical constituents of the essential oil (EO) of its leaves and inflorescence were documented. However, no data about the chemical compositions of other parts of the EOs of the plant have been reported to date. Moreover, there are no previous biological activity reports on any parts of the EOs of this plant. Thus, in this study, the EOs were isolated from the stem bark and roots of this plant by hydrodistillation and analyzed using gas chromatography-mass spectrometry to identify their components. In addition, antibacterial potentials of the oils were evaluated using the disc diffusion and minimal inhibitory concentration (MIC) methods. 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide methods were also employed to assess their antioxidant properties. Oxygenated monoterpenes (71.82% and 77.51%), of which 2,5-dimethoxy- p -cymene (57.28% and 64.76%) and thymol methyl ether (9.51% and 8.93%) were identified as major components in the EOs of stem bark and roots of L. tomentosa and the oils, were the most potent in the DPPH (IC50, 0.33 ± 1.10 and 0.39 ± 0.97 mg/mL) assay, respectively. Moreover, the EOs demonstrated appreciable activity towards the gram+ ( S. aureus and B. cereus ) bacteria. Among these oils, the oil of the stem bark showed the greatest activity to the gram+ (MIC = 0.625 mg/mL) bacteria. Therefore, the overall results suggested that the EOs of L. tomentosa may be a promising prospect for pharmaceutical, food, and other industrial applications.