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The authors present a case of an 85-year-old male patient with multiple co-morbidities. He underwent laparotomy for carcinoma rectum, recovered from anesthesia, and was shifted to the ward. On sixth day his condition deteriorated, so was shifted to ICU. In ICU, he was put on ventilator in ASV mode, and fentanyl infusion started. The next morning a high VT of 900-1000 mL was noticed to be delivered, while the respiratory rate was 8-10/min. Naloxone administration eased the respiratory parameters. Careful monitoring of sedation levels and respiratory drive becomes crucial for preventing volutrauma in ASV mode of ventilation. [ABSTRACT FROM AUTHOR]

The three medicinal herbs, Curcumalonga, Curcuma caesia and Curcuma aromatica of family Zingiberaceae are highly valued worldwide for their high medicinal value and economic significance. The detail of phytochemical and pharmacological importance of Curcuma longa has been well explored, in contrast to C. caesia and C. aromatica. In the present investigation the phytochemical and pharmacological importance of other two species C. caesia and C. aromatica has been explored and compared with C. longa. Extracts were prepared from the rhizomes of all three varieties by successive extraction procedure with different solvents with increasing polarity. Phytochemical evaluation were performed by total phenol content (TPC), total flavonoid content (TFC) and other qualitative assay. Antioxidant activity of the rhizome extracts were evaluated by different in vitro assays viz. DPPH, ABTS, FRAP etc. The antimicrobial activity was performed by the agar well diffusion method against different pathogenic microorganisms. The different solvent fractions of all three Curcuma species showed varying antioxidant and antimicrobial activity. C. aromatica and C. longa have higher antioxidant potential as compare to C. caesia and C. aromatica have high potential of antimicrobial activity. Ethanol and Methanol extract of rhizomes of all three species have great potential of antioxidant activity. C. aromatica ethanol extract showed highest activity in DPPH, FRAP, TRP and also highest phenol content. Thus all the species of curcuma are capable of retarding oxidative stress and damage by free radicals so these ethno medicinal plants can be used as a potent natural antioxidant and antibiotic drug. [ABSTRACT FROM AUTHOR]

The article discusses a study which detected the presence of SARS-CoV-2 viral RNA in toothbrushes. Topics include how the presence of SARS-CoV-2 RNA was detected, sensitivity of toothbrushes which is comparable to the sensitivities reported with saliva, and conclusion on the role of toothbrushes as sampling methodology for the detection of SARS-CoV-2.

Temporal prefetchers are powerful because they can prefetch irregular sequences of memory accesses, but temporal prefetchers are commercially infeasible because they store large amounts of metadata in DRAM. This article presents Triage, the first temporal data prefetcher that does not require off-chip metadata. Triage builds on two insights: (1) Metadata are not equally useful, so the less useful metadata need not be saved, and (2) for irregular workloads, it is more profitable to use portions of the LLC to store metadata than data. We also introduce novel schemes to identify useful metadata, to compress metadata, and to determine the fraction of the LLC to dedicate for metadata. Using an industrial-strength simulator running irregular workloads on a single-core system, we show that at a prefetch degree of 4, Triage improves performance by 41.1 percent compared to a baseline with no prefetching, whereas BO, a state-of-the-art prefetcher that uses only on-chip metadata, sees only 10.9 percent improvement. Compared with MISB, a temporal prefetcher that uses off-chip metadata, Triage provides a design alternative that reduces memory traffic by an order of magnitude (260.8 percent extra traffic for MISB at degree 1 versus 56.9 percent for Triage), while reducing coverage by 20 percent. [ABSTRACT FROM AUTHOR]

In multicellular organisms, the specification, coordination, and compartmentalization of cell types enable the formation of complex body plans. However, some eukaryotic protists such as slime molds generate diverse and complex structures while remaining in a multinucleate syncytial state. It is unknown if different regions of these giant syncytial cells have distinct transcriptional responses to environmental encounters and if nuclei within the cell diversify into heterogeneous states. Here, we performed spatial transcriptome analysis of the slime mold Physarum polycephalum in the plasmodium state under different environmental conditions and used single-nucleus RNA-sequencing to dissect gene expression heterogeneity among nuclei. Our data identifies transcriptome regionality in the organism that associates with proliferation, syncytial substructures, and localized environmental conditions. Further, we find that nuclei are heterogenous in their transcriptional profile and may process local signals within the plasmodium to coordinate cell growth, metabolism, and reproduction. To understand how nuclei variation within the syncytium compares to heterogeneity in single-nucleus cells, we analyzed states in single Physarum amoebal cells. We observed amoebal cell states at different stages of mitosis and meiosis, and identified cytokinetic features that are specific to nuclei divisions within the syncytium. Notably, we do not find evidence for predefined transcriptomic states in the amoebae that are observed in the syncytium. Our data shows that a single- celled slime mold can control its gene expression in a region-specific manner while lacking cellular compartmentalization and suggests that nuclei are mobile processors facilitating local specialized functions. More broadly, slime molds offer the extraordinary opportunity to explore how organisms can evolve regulatory mechanisms to divide labor, specialize, balance competition with cooperation, and perform other foundational principles that govern the logic of life. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine if oranges in the top and bottom layers within a Standard Place Pack were impacted differently by irradiation after long-term storage. ‘Barnfield’ Navel oranges were packed in Standard Place Pack cartons and treated with 0, 0.15, or 1 kGy of gamma irradiation. The fruit were stored for 3 weeks at 5 °C and then for 1 week at 20 °C. After storage, the fruit from the top and bottom layers were separately evaluated for quality. The development of stem-end rind breakdown (SERB) was the main cause of quality loss and was greater in irradiated fruit in the top layer. Fruit in the bottom layer showed more physical damage (flattening) but lower incidence of SERB. The changes in individual sugar content were minimal but significant for layer. The content of individual organic acids was consistently lower in irradiated fruit from the bottom layer. Layer type showed a stronger effect on phenolic compounds than irradiation dose. The tristimulus color, total soluble solids, titratable acidity, and firmness of fruit were not influenced by irradiation dose or layer type. The results show that damage in irradiated Navel oranges depends on dose and layer, with the top layers showing greater physiological damage and bottom layers showing more physical damage. [ABSTRACT FROM AUTHOR]

Transnational trade of ‘Seedless Kishu’ mandarins ( Citrus kinokuni mukakukishu ) would require them to be subjected to a suitable phytosanitary treatment. Irradiation is used as an effective treatment for many fruit, but the effect on quality of kishu mandarins is unknown. ‘Seedless Kishu’ mandarins were treated with gamma irradiation (150, 400, and 1000 Gy) and stored for three weeks at 6 °C and then for one week at 20 °C. Irradiation at 400 and 1000 Gy promoted browning of the calyx end and fungal infection. Irradiation caused immediate reductions in pulp firmness, vitamin E, individual sugars and carotenoids but increased the content of organic acids, except ascorbic acid, and phenolic compounds. The volatile profile of tested fruit was also differentially altered by irradiation. Most of these initial changes were dose dependent. ’Seedless Kishu’ mandarins are significantly sensitive to irradiation and are not suitable for treatment at the studied doses. [ABSTRACT FROM AUTHOR]

The assembly of microtubule-based cytoskeleton propels the cilia and flagella growth. Previous studies have indicated that the kinesin-2 family motors transport tubulin into the cilia through intraflagellar transport. Here, we report a direct interaction between the C-terminal tail fragments of heterotrimeric kinesin-2 and α-tubulin1 isoforms in vitro. Blot overlay screen, affinity purification from tissue extracts, cosedimentation with subtilisin-treated microtubule and LC-ESI-MS/ MS characterization of the tail-fragment-associated tubulin identified an association between the tail domains and α- tubulin1A/D isotype. The interaction was confirmed by Forster's resonance energy transfer assay in tissue-cultured cells. The overexpression of the recombinant tails in NIH3T3 cells affected the primary cilia growth, which was rescued by coexpression of a α-tubulin1 transgene. Furthermore, fluorescent recovery after photobleach analysis in the olfactory cilia of Drosophila indicated that tubulin is transported in a non-particulate form requiring kinesin-2. These results provide additional new insight into the mechanisms underlying selective tubulin isoform enrichment in the cilia. [ABSTRACT FROM AUTHOR]

Drugs of abuse induce persistent remodeling of reward circuit function, a process thought to underlie the emergence of drug craving and relapse to drug use. However, how circuit-specific, drug-induced molecular and cellular plasticity can have distributed effects on the mesolimbic dopamine reward system to facilitate relapse to drug use is not fully elucidated. Here, we demonstrate that dopamine receptor D3 (DRD3)-dependent plasticity in the ventral pallidum (VP) drives potentiation of dopamine release in the nucleus accumbens during relapse to cocaine seeking after abstinence. We show that two distinct VP DRD3+ neuronal populations projecting to either the lateral habenula (LHb) or the ventral tegmental area (VTA) display different patterns of activity during drug seeking following abstinence from cocaine self-administration and that selective suppression of elevated activity or DRD3 signaling in the LHb-projecting population reduces drug seeking. Together, our results uncover how circuit-specific DRD3-mediated plasticity contributes to the process of drug relapse. • DRD3-mediated plasticity in the VP drives post-abstinence cocaine-seeking behavior • VP DRD3 signaling regulates dopamine release in the NAc latSh during seeking • VP DRD3+ projections to the LHb and VTA display differing activity during seeking • DRD3 signaling/activity of LHb-projecting VP DRD3+ neurons drives seeking behavior Pribiag et al. show that ventral pallidum dopamine receptor D3 signaling regulates drug seeking following prolonged abstinence from cocaine self-administration via activation of a subpopulation of neurons projecting to the lateral habenula. This regulation feeds back to influence dopamine release in the lateral shell of the nucleus accumbens during drug seeking. [ABSTRACT FROM AUTHOR]

Due to deleterious health effects, consumption of trans fat containing fried foods is a major concern. The present study has assessed total fat, SFA, cis- UFA and TFA content of Indian fried foods- French fries, Poori , Potato chips , Bread Pakora and Mathri ( on dry weight basis ), at varying number of frying cycles/temperatures as well as composition of the oils extracted from the foods and the oils used for frying. Total fat in the food items was significantly higher at 32nd (x̄27.4%) versus the 1st frying cycle (x̄22.5%; p  < 0.05). Progressive frying cycles (1st vs. 32nd)/temperatures demonstrated declining levels of cis- UFAs (at 180 °C: x̄16.33% vs. x̄11.29%; at 160 °C: x̄19.54% vs. x̄13.81%) with concomitant increase in SFA (at 180 °C: x̄4.97% vs. x̄14.97%; at 160 °C: x̄5.19% vs. x̄13.79%) and TFA content (at 180 °C: x̄0.05% vs. x̄0.89%; at 160 °C: x̄0.04% vs. x̄0.17%). Compared to the unheated oil, at 32nd frying cycle (irrespective of the frying temperatures), oils extracted from fried foods registered a significant decrease in cis- UFA (x̄17.41%) coupled with an increase in SFA (x̄63.74%) and an exponential increase in TFA (39-301 folds); however, the change was slightly lesser in oils used for frying ( cis- UFA: x̄15.06%; SFA: x̄53.75%; TFA: 20-264 folds). To curb TFA in fried foods, necessary regulations are needed for restricting the number of frying cycles as well as the frying temperatures along with awareness generation regarding appropriate frying practices., Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05989-z., Competing Interests: Conflict of interestThe authors declare that they have no competing interests., (© Association of Food Scientists & Technologists (India) 2024. 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.)

Maize yield is threatened by increasing incidences of head smut disease caused by Sporisorium reilianum . To help breeders identify S. reilianum -resistant maize lines, the availability of efficient screening systems would be an advantage. Here we assessed maize lines with distinct levels of field resistance against head smut disease in greenhouse experiments using two different inoculation techniques. Addition of mixtures of mating-compatible sporidia to the soil at seedling stage of the plant did not lead to plant disease, and we could detect only marginal amounts of fungal DNA in apical meristems at eighteen days after sowing. Inoculation of the maize lines by leaf-whorl inoculation led to both high disease incidence and prominent levels of fungal DNA in apical meristems in all tested maize lines regardless of their field resistance levels. Thus, S. reilianum entering the plant via the leaf whorl can escape existing resistance mechanisms of currently known field-resistant maize lines. Since field-resistant lines are also resistant to inoculation via teliospore-contaminated soil, we propose teliospore addition to seeds at the time of sowing (rather than leaf-whorl inoculation of seedlings) combined with quantitative detection of fungal DNA in apical meristems, as an efficient screening procedure to discover field-resistant lines. However, screening maize plants for resistance against the leaf-whorl inoculation method might be promising for the discovery of novel resistance mechanisms needed to develop durably resistant maize lines.

Cells assemble fibronectin, the major extracellular matrix (ECM) protein, into fibrillar matrices, which serve as 3D architectural scaffolds to provide, together with other ECM proteins tissue-specific environments. Although recent approaches enable to bioengineer 3D fibrillar fibronectin matrices in vitro, it remains elusive how fibronectin can be co-assembled with other ECM proteins into complex 3D fibrillar matrices that recapitulate tissue-specific compositions and cellular responses. Here, we introduce the engineering of fibrillar fibronectin-templated 3D matrices that can be complemented with other ECM proteins, including vitronectin, collagen, and laminin to resemble ECM architectures observed in vivo. For the co-assembly of different ECM proteins, we employed their innate fibrillogenic mechanisms including shear forces, pH-dependent electrostatic interactions, or specific binding domains. Through recapitulating various tissue-specific ECM compositions and morphologies, the large scale multi-composite 3D fibrillar ECM matrices can guide fibroblast adhesion, 3D fibroblast tissue formation, or tissue morphogenesis of epithelial cells. In other examples, we customize multi-composite 3D fibrillar matrices to support the growth of signal propagating neuronal networks and of human brain organoids. We envision that these 3D fibrillar ECM matrices can be tailored in scale and composition to modulate tissue-specific responses across various biological length scales and systems, and thus to advance manyfold studies of cell biological systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tuberculosis (TB) is one of the leading causes of death world-wide after AIDS. It infects around one-third of global population and approximately two million people die annually from this disease because it is a very contagious disease spread by Mycobacterium tuberculosis . The increasing number of drug-resistant strains and the failure of conventional treatments against this strain are the challenges of the coming decades. New therapeutic techniques aim to confirm cure without deterioration, to reduce deaths, contagions and the formation of drug-resistant strains. A plethora of new diagnostic tests are available to diagnose the active tuberculosis, screen latent M. tuberculosis infection, and to identify drug-resistant strains of M. tuberculosis . When effective prevention strategies do not prevail, high rates of early case detection and successive cures to control TB emergence would not be possible. In this review, we discussed the structural features of M. tuberculosis , Multi drug resistance tuberculosis (MDR-TB), extremely drug-resistant tuberculosis (XDR-TB), the mechanism of M. tuberculosis infection, the mode of action of first and second-line antitubercular drugs, the mechanism of resistance to the existing drugs, compounds in preclinical and clinical trial and drugs presently available for the treatment of tuberculosis. Moreover, the new diagnostic techniques to detect M. tuberculosis are also discussed in this review., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cell cycle control is a central aspect of the biology of proliferating eukaryotic cells. However, progression through the cell cycle relies on a highly complex network, making it difficult to unravel the core design principles underlying the mechanisms that sustain cell proliferation and the ways in which they interact with other cellular pathways. In this context, the use of a synthetic approach to simplify the cell cycle network in unicellular genetic models such as fission yeast has opened the door to studying the biology of proliferating cells from unique perspectives. Here, we provide a series of methods based on a minimal cell cycle module in the fission yeast Schizosaccharomyces pombe that allows for an unprecedented artificial control of cell cycle events, enabling the rewiring and remodeling of cell cycle progression., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Ossicular reconstruction with autologous materials has been practised for a long time, but the procedure may lead to stiffness of joints and bony ankyloses thus hampering the sound conduction mechanism. This paper describes a novel technique of creating joint capsule around the reconstructed joints with temporalis fascia strips hoping a firm and movable union with full functional restoration., Materials & Methods: This study is a prospective study of 35 patients requiring tympanomastoid surgery with ossicular reconstruction and were studied over a period of 2 years. The newly reconstructed ossicular joints were wrapped with temporalis fascia strips. Post-operatively air-bone gap closure were studied and statistically analysed., Results: A significant air-bone gap closure was achieved in 23 patients, while moderate improvement was seen in remaining cases. Only 1 patient had tympanic membrane graft failure and rest all had well healed tympanic membrane., Conclusion: Fascial arthroplastic ossiculoplasty is a simple and safe procedure and the results are reproducible and more predictable. It provides an ossicular assembly which is near to normal in its physiological functions., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© 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.)

Background: Platelet-rich fibrin (PRF) is a second-generation platelet concentrate with multiple applications in wound healing and regeneration in both periodontitis and diabetes. However, the three dimensional (3-D) structure and cytokine content of PRF might be altered in patients suffering from either/both of the chronic inflammatory conditions, ultimately influencing the efficacy of PRF as a biomaterial for regenerative medicine., Aim: The aim of the present study was hence to evaluate the effect of both these chronic inflammatory diseases on the 3-D structure of PRF membrane. An attempt was also made to compare the growth factor content between the plasma and RBC ends of the prepared PRF gel., Materials & Methods: L-PRF was prepared for twenty participants, healthy (5), periodontitis (5), T2DM (5) and T2DM with periodontitis (5). Porosity and fiber diameter of PRF membranes was visualized under FE-SEM and measured using ImageJ Software. PDGF-BB and TGF-β1 levels in PRF gel were assessed by ELISA., Results: The average diameter of fibrin fibers under FE-SEM was 0.15 to 0.30 micrometers. Porosity was higher at the plasma end (p = 0.042). Red blood cell (RBC) end of the membrane had thinner fibers arranged in a comparatively more dense and compact structure with smaller porosities. Healthy subjects had the least porous PRF compared to subjects with either/both of the chronic conditions. PDGF-BB levels were similar along all the four groups. TGF-β1 levels were highest in healthy subjects., Discussion: 3-D structure and growth factor content of PRF are influenced by a person's periodontal and/or diabetic status. The RBC end of the PRF membrane, as compared to the plasma end, has thinner fibers arranged in a comparatively more dense and compact structure with smaller porosities, and hence should be favored during periodontal regenerative procedures., Conclusion: Both periodontitis and diabetes have a significant influence on the 3-D structure and growth factor content of PRF produced., (© 2022 Wiley Periodicals LLC.)

Self-organizing neural organoids grown from pluripotent stem cells 1-3 combined with single-cell genomic technologies provide opportunities to examine gene regulatory networks underlying human brain development. Here we acquire single-cell transcriptome and accessible chromatin data over a dense time course in human organoids covering neuroepithelial formation, patterning, brain regionalization and neurogenesis, and identify temporally dynamic and brain-region-specific regulatory regions. We developed Pando-a flexible framework that incorporates multi-omic data and predictions of transcription-factor-binding sites to infer a global gene regulatory network describing organoid development. We use pooled genetic perturbation with single-cell transcriptome readout to assess transcription factor requirement for cell fate and state regulation in organoids. We find that certain factors regulate the abundance of cell fates, whereas other factors affect neuronal cell states after differentiation. We show that the transcription factor GLI3 is required for cortical fate establishment in humans, recapitulating previous research performed in mammalian model systems. We measure transcriptome and chromatin accessibility in normal or GLI3-perturbed cells and identify two distinct GLI3 regulomes that are central to telencephalic fate decisions: one regulating dorsoventral patterning with HES4/5 as direct GLI3 targets, and one controlling ganglionic eminence diversification later in development. Together, we provide a framework for how human model systems and single-cell technologies can be leveraged to reconstruct human developmental biology., (© 2022. The Author(s).)

Experimental evolution using fast-growing unicellular organisms is a unique strategy for deciphering the principles and mechanisms underlying evolutionary processes as well as the architecture and wiring of basic biological functions. Over the past decade, this approach has benefited from the development of powerful systems for the continuous control of the growth of independently evolving cultures. While the first devices compatible with multiplexed experimental evolution remained challenging to implement and required constant user intervention, the recently developed eVOLVER framework represents a fully automated closed-loop system for laboratory evolution assays. However, it remained difficult to maintain and compare parallel evolving cultures in tightly controlled environments over long periods of time using eVOLVER. Furthermore, a number of tools were lacking to cope with the various issues that inevitably occur when conducting such long-term assays. Here we present a significant upgrade of the eVOLVER framework, providing major modifications of the experimental methodology, hardware and software as well as a new stand-alone protocol. Altogether, these adaptations and improvements make the eVOLVER a versatile and unparalleled set-up for long-term experimental evolution.

Background: Cancer is a deadly disease responsible for worldwide mortality; usually, middle- and low-income countries have been more affected by cancer and are responsible for 70% of deaths. The present study was performed with the aim to design silver nanoparticles using three species of Curcuma, i.e., Curcuma longa, Curcuma aromatica, and Curcuma caesia., Methods: The rhizomes of different plants were extracted with ethanol. The rhizome extracts were used to prepare silver nanoparticles. It was optimized at different pH, silver ion concentrations, and concentrations of plant extracts. The anticancer activity of prepared nanoparticles of C. longa, C. aromatica, and C. caesia was evaluated on a human colon cancer cell line (HT-29) using sulforhodamine B (SRB) assay., Results: The percentage yield of C. longa, C. aromatica, and C. caesia was 11.34 g, 15.45 g, and 12.67 g, respectively. The results exhibited that the prepared nanoparticles were smooth and spherical. All the nanoparticles of rhizome extracts rescued the viability of HT-29 cells in a different extent. HT-29 cells were sensitive to prepared nanoparticles that induce more cytotoxicity towards cancer cells., Conclusion: Thus, the prepared silver nanoparticle of Curcuma species through green synthesis may help treat cancer with low toxicity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Erlotinib is a first generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) which was granted Food and Drug administration (FDA) approval for treatment of patients with locally advanced or metastatic NSCLC. The present study aimed at development of radiolabeled erlotinib variants as tyrosine kinase inhibitors. Three DOTA-erlotinib conjugates were prepared for radiolabeling with 177 Lu. The terminal alkyne group of erlotinib was modified by performing Cu-catalyzed click chemistry and three different linkers were introduced which were then conjugated to the chelator, DOTA. The DOTA-erlotinib conjugates were characterized by 1 H NMR and ESI-MS. 177 Lu-DOTA-erlotinib complexes were characterized using nat Lu-DOTA-erlotinib conjugates. The 177 Lu-complexes exhibited high in vitro stability in human serum up to 48 h. They were highly hydrophilic in nature as observed from their log P o/w values ( 177 Lu-DOTA-propyl-Er: -2.5 ± 0.1; 177 Lu-DOTA-PEG 3 -Er: -3.0 ± 0.1; 177 Lu-DOTA-PEG 6 -Er: -3.3 ± 0.1). The MTT assay in A431 human epidermoid carcinoma cell lines indicates that the chemical modification at the terminal alkyne group of the erlotinib molecule does not have significant effect on its TKI property. Biodistribution studies in normal Swiss mice demonstrated fast clearance and excretion of 177 Lu-labeled erlotinib complexes. These studies indicate that erlotinib variants with hydrophobic pharmacokinetic modifiers/chelators may enhance the retention of 177 Lu-labeled complexes in blood thereby increasing the probability to reach EGFR-expressing tumor., 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 © 2022 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to validate an active matrix metalloproteinase (MMP-8) point-of-care diagnostic tool in COVID-19 patients with periodontal disease., Subjects, Materials, and Methods: Seventy-two COVID-19-positive and 30 COVID-19-negative subjects were enrolled in the study. Demographic data were recorded, periodontal examination carried out, and chairside tests run for evaluating the expression of active MMP-8 (aMMP-8) in the site with maximum periodontal breakdown via gingival crevicular fluid sampling as well as via a mouth rinse-based kit for general disease activity. In COVID-19-positive patients, the kits were run again once the patients turned COVID-19 negative., Results: The overall (n = 102) sensitivity/specificity of the mouthrinse-based kits to detect periodontal disease was 79.41%/36.76% and that of site-specific kits was 64.71%/55.88% while adjusting for age, gender, and smoking status increased the sensitivity and specificity (82.35%/76.47% and 73.53%/88.24, respectively). Receiver operating characteristic (ROC) analysis for the adjusted model revealed very good area under the ROC curve 0.746-0.869 (p < .001) and 0.740-0.872 (p < .001) (the aMMP-8 mouth rinse and site-specific kits, respectively). No statistically significant difference was observed in the distribution of results of aMMP-8 mouth rinse test (p = .302) and aMMP-8 site-specific test (p = .189) once the subjects recovered from COVID-19., Conclusions: The findings of the present study support the aMMP-8 point-of-care testing (PoCT) kits as screening tools for periodontitis in COVID-19 patients. The overall screening accuracy can be further increased by utilizing adjunctively risk factors of periodontitis. The reported noninvasive, user-friendly, and objective PoCT diagnostic methodology may provide a way of stratifying risk groups, deciding upon referrals, and in the institution of diligent oral hygiene regimens., (© 2022 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Cells exist in an astonishing range of volumes across and within species. However, our understanding of cell size control remains limited, owing in large part to the challenges associated with accurate determination of cell volume. Much of our comprehension of size regulation derives from yeast models, but even for these morphologically stereotypical cells, assessment of cell volume has mostly relied on proxies and extrapolations from two-dimensional measurements. Recently, the fluorescence exclusion method (FXm) was developed to evaluate the size of mammalian cells, but whether it could be applied to smaller cells remained unknown. Using specifically designed microfluidic chips and an improved data analysis pipeline, we show here that FXm reliably detects subtle differences in the volume of fission yeast cells, even for those with altered shapes. Moreover, it allows for the monitoring of dynamic volume changes at the single-cell level with high time resolution. Collectively, our work highlights how the coupling of FXm with yeast genetics will bring new insights into the complex biology of cell growth., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Induced pluripotent stem cell (iPSC)-derived organoids provide models to study human organ development. Single-cell transcriptomics enable highly resolved descriptions of cell states within these systems; however, approaches are needed to directly measure lineage relationships. Here we establish iTracer, a lineage recorder that combines reporter barcodes with inducible CRISPR-Cas9 scarring and is compatible with single-cell and spatial transcriptomics. We apply iTracer to explore clonality and lineage dynamics during cerebral organoid development and identify a time window of fate restriction as well as variation in neurogenic dynamics between progenitor neuron families. We also establish long-term four-dimensional light-sheet microscopy for spatial lineage recording in cerebral organoids and confirm regional clonality in the developing neuroepithelium. We incorporate gene perturbation (iTracer-perturb) and assess the effect of mosaic TSC2 mutations on cerebral organoid development. Our data shed light on how lineages and fates are established during cerebral organoid formation. More broadly, our techniques can be adapted in any iPSC-derived culture system to dissect lineage alterations during normal or perturbed development., (© 2021. The Author(s).)

Design Randomised prospective double-blind study.Case selection Thirty-seven chronic periodontitis patients were randomly prescribed either saltwater (n = 17) or chlorhexidine (n = 20) mouth rinse following open flap debridement. Gingival Index (GI), post-operative pain, mouth rinse satisfaction, matrix metalloproteinase activity and tasting were assessed at baseline, one week and 12 weeks.Data analysis Inter-group and intra-group comparisons were done for all the parameters recorded at different time intervals using Friedman, Wilcoxon signed-rank and Mann-Whitney U tests. P value less than 0.05 was considered statistically significant.Results There was a statistically significant decrease in GI from baseline to week 1/week 12 following surgery in both the groups. However, there was no significant difference between the groups at any time point.Conclusions Saltwater rinses are as efficient as 0.12% chlorhexidine in reducing inflammation following minimal invasive periodontal surgery. Being an inexpensive and easily accessible option, it might be considered the mouth rinse of choice during the early stages of wound healing., (© 2021. The Author(s), under exclusive licence to the British Dental Association.)

The cilium, the sensing centre for the cell, displays an extensive repertoire of receptors for various cell signalling processes. The dynamic nature of ciliary signalling indicates that the ciliary entry of receptors and associated proteins must be regulated and conditional. To understand this process, we studied the ciliary localisation of the odour-receptor coreceptor (Orco), a seven-pass transmembrane protein essential for insect olfaction. Little is known about when and how Orco gets into the cilia. Here, using Drosophila melanogaster, we show that the bulk of Orco selectively enters the cilia on adult olfactory sensory neurons in two discrete, one-hour intervals after eclosion. A conditional loss of heterotrimeric kinesin-2 during this period reduces the electrophysiological response to odours and affects olfactory behaviour. We further show that Orco binds to the C-terminal tail fragments of the heterotrimeric kinesin-2 motor, which is required to transfer Orco from the ciliary base to the outer segment and maintain within an approximately four-micron stretch at the distal portion of the ciliary outer-segment. The Orco transport was not affected by the loss of critical intraflagellar transport components, IFT172/Oseg2 and IFT88/NompB, respectively, during the adult stage. These results highlight a novel developmental regulation of seven-pass transmembrane receptor transport into the cilia and indicate that ciliary signalling is both developmentally and temporally regulated., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The mental health of perimenopausal and postmenopausal women is a relatively understudied area. This review formally explores the prevalence of depression in perimenopausal and postmenopausal women in India., Methods: Databases like PubMed, Embase, Cochrane library, Web of Science and Scopus were systematically searched for cross-sectional or cohort studies, providing prevalence of depression in Indian perimenopausal and postmenopausal women. Systematic study selection and data extraction procedures were followed. Quality assessment of individual study was done using AXIS tool. For pooling of effect sizes, the random effects model was used. Funnel plot and Egger's test were used to ascertain publication bias. Subgroup analyses and meta-regression analysis were used to explore heterogeneity in the summary estimates., Results: After a thorough search, ten studies were found to be eligible and included in this review. Pooled estimate for prevalence of depression (random effects model) in perimenopausal and postmenopausal women in India is 42.47 % (95 % CI: 28.73-57.49, I 2 = 97.7 %). On visual inspection of the funnel plot and interpreting egger's test (bias: 3.49, SE bias: 3.68, p = 0.37), there was absence of publication bias., Conclusion: We documented 42.47 % pooled prevalence of depression in perimenopausal and postmenopausal women in India., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Previous studies have suggested excess GH/IGF1 secretion in patients with acromegaly is protective for periodontal health. Diabetes is prevalent comorbidity in patients of acromegaly and is associated with worsening of periodontal disease. The present study evaluates the periodontal health and cytokines status in treatment-naive active acromegaly patients with and without diabetes. Eleven patients, each of acromegaly with and without diabetes and 20 healthy controls were enrolled. Periodontal parameters were assessed. GCF and blood samples for IL-6, TGF-β1, and PDGF were obtained. Serum GH, IGF1, HbA1c, pituitary hormones and MRI sella were performed in patients with acromegaly. There was no significant difference in periodontal status of patients with acromegaly and healthy controls. However, a significant increase in serum IL-6 (p = 0.019) and TGF-β1 (p = 0.025) levels in patients with acromegaly was observed and all patients had concurrent hypogonadism. Nevertheless, the patients with acromegaly having diabetes had modestly higher CAL and PD and serum IL-6 levels (p = 0.051), but it could not exert adverse effects on periodontal health in presence of GH/IGF1 excess. GH/IGF1 excess did not exert a protective effect on periodontal status in acromegaly, possibly due to concurrent hypogonadism and opposing cytokines; however, it could mask the ill-effects of diabetes on periodontal health.

During gastrulation, physical forces reshape the simple embryonic tissue to form the complex body plans of multicellular organisms 1 . These forces often cause large-scale asymmetric movements of the embryonic tissue 2,3 . In many embryos, the gastrulating tissue is surrounded by a rigid protective shell 4 . Although it is well-recognized that gastrulation movements depend on forces that are generated by tissue-intrinsic contractility 5,6 , it is not known whether interactions between the tissue and the protective shell provide additional forces that affect gastrulation. Here we show that a particular part of the blastoderm tissue of the red flour beetle (Tribolium castaneum) tightly adheres in a temporally coordinated manner to the vitelline envelope that surrounds the embryo. This attachment generates an additional force that counteracts tissue-intrinsic contractile forces to create asymmetric tissue movements. This localized attachment depends on an αPS2 integrin (inflated), and the knockdown of this integrin leads to a gastrulation phenotype that is consistent with complete loss of attachment. Furthermore, analysis of another integrin (the αPS3 integrin, scab) in the fruit fly (Drosophila melanogaster) suggests that gastrulation in this organism also relies on adhesion between the blastoderm and the vitelline envelope. Our findings reveal a conserved mechanism through which the spatiotemporal pattern of tissue adhesion to the vitelline envelope provides controllable, counteracting forces that shape gastrulation movements in insects.

Introduction: The aim of this work was to understand how patients with non-alcoholic steatohepatitis (NASH) perceive their disease, unmet needs, and expectations regarding future treatment through online bulletin board (OBB) qualitative research., Methods: OBB is an asynchronous online qualitative market research tool that provides an open forum for interactive discussion among participants. Patients with NASH were recruited via physician referral and completed a screener questionnaire to ensure their eligibility and willingness to participate. A trained moderator managed the discussion that allowed open answers and responses to other participants' posts. Patient responses were analyzed using a combination of different qualitative analytical tools., Results: The OBB ran for 4 days and included 16 patients (n = 8, UK; n = 8, US) with NASH (fibrosis stages F1-F3) and comorbidities including diabetes/prediabetes (n = 9) and obesity (n = 12). The key insights were (1) patients with NASH have a poor understanding of the disease, its progression, and management-they feel a lack of adequate educational support from their physicians; (2) diagnosis of NASH is incidental in most cases, mainly because patients fail to spontaneously associate their signs or symptoms with their liver condition; (3) comorbidities (obesity and diabetes) are more concerning to patients than NASH; and (4) patients perceive that NASH impacts their social life and work performance in more advanced stages., Conclusions: This OBB provided valuable patient insights into NASH disease perception and management and revealed unmet need areas. In light of no approved therapies, these patient insights can inform early drug development strategies and stakeholder discussions on NASH., Funding: Novartis Pharma AG, Basel.

Fluorescence microscopy is a key driver of discoveries in the life sciences, with observable phenomena being limited by the optics of the microscope, the chemistry of the fluorophores, and the maximum photon exposure tolerated by the sample. These limits necessitate trade-offs between imaging speed, spatial resolution, light exposure, and imaging depth. In this work we show how content-aware image restoration based on deep learning extends the range of biological phenomena observable by microscopy. We demonstrate on eight concrete examples how microscopy images can be restored even if 60-fold fewer photons are used during acquisition, how near isotropic resolution can be achieved with up to tenfold under-sampling along the axial direction, and how tubular and granular structures smaller than the diffraction limit can be resolved at 20-times-higher frame rates compared to state-of-the-art methods. All developed image restoration methods are freely available as open source software in Python, FIJI, and KNIME.

This work evaluates the potential of a 68 Ga labeled long chain 16C fatty acid for cardiac metabolic imaging. For radiolabeling with 68 Ga, hexadecanedioic acid was coupled with the chelator p-NH 2 -Bn-NOTA. Under the optimized conditions, NOTA-hexadecanoic acid could be radiolabeled with 68 Ga in ≥95% yields. In biodistribution studies carried out in Swiss mice, 68 Ga-NOTA-hexadecanoic acid showed low myocardial uptake at 2 min p.i. (3.7 ± 1.3%ID/g). While 68 Ga-NOTA-hexadecanoic acid cleared rapidly from non-target organs such as blood, lungs, intestine and kidney, wash out from liver was slow. Radio-HPLC analyses of myocardial extracts of rats injected with 68 Ga-NOTA-hexadecanoic acid confirmed its metabolic transformation in the myocardium., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: The present paper reports a systematic study on the effect of bifunctional chelators (BFC) namely, NOTA, DOTA, and DTPA, on the radiochemical formulation, in vitro stability, and in vivo biological properties of 68 Ga-labeled RGD peptide derivatives., Methods: The three RGD conjugates namely, NOTA-Bn-E-[c(RGDfk)] 2 , DOTA-Bn-E-[c(RGDfk)] 2 , and DTPA-Bn-E-[c(RGDfk)] 2 were radiolabeled with 68 Ga and the radiolabeling was optimized with respect to the ligand amount, radiolabeling time, and temperature. Further, the 68 Ga complexes were assessed for their in vitro and in vivo stabilities. The biodistribution studies of the three radiolabeled conjugates were carried out in C57BL/6 mice bearing melanoma tumor at 30 min and 1 h post-adimistration., Results: NOTA-Bn-E-[c(RGDfk)] 2 could be radiolabeled with 68 Ga at room temperature while DOTA-Bn-E-[c(RGDfk)] 2 and DTPA-Bn-E-[c(RGDfk)] 2 were radiolabeled at high temperature. 68 Ga-NOTA-Bn-E-[c(RGDfk)] 2 was found to be the most kinetically rigid in in vitro stability assay. The uptake of the three radiolabeled peptide conjugates in melanoma tumor was comparable at 1 h post-administration (NOTA; DOTA; DTPA (% I.D./g):: 2.78 ± 0.38; 3.08 ± 1.1; 3.36 ± 0.49). However, the tumor/background ratio of 68 Ga-NOTA-Bn-E-[c(RGDfk)] 2 was the best amongst the three radiotracers. 68 Ga-complexes of NOTA-Bn-E-[c(RGDfk)] 2 and DOTA-Bn-E-[c(RGDfk)] 2 showed excellent in vivo stability while 68 Ga-DTPA-Bn-E-[c(RGDfk)] 2 showed significant metabolic degradation., Conclusion: These studies show that 68 Ga-NOTA-Bn-E-[c(RGDfk)] 2 would be the most appropriate 68 Ga-labeled radiotracer and the most amenable for kit formulation., Competing Interests: Compliance with Ethical StandardsAkanksha Jain, Sudipta Chakraborty, Haladhar Dev Sarma and Ashutosh Dash, declare that they have no conflict of interest financial, scientific or otherwise in the publication of this article. Research at the Bhabha Atomic Research Centre (BARC) is part of the ongoing activities of the Department of Atomic Energy, India and is fully supported by government funding.All procedures performed in studies involving animals were in strict compliance with the approved protocols of Institutional Animal Ethics Committee of BARC, India.The institutional review board of our institute, BARC, approved this retrospective study, and the requirement to obtain informed consent was waived.

Present work evaluates the potential of a newly synthesized (68)Ga-NOTA-folic acid conjugate for PET imaging of tumors over-expressing folate receptors (FRs). NOTA-folic acid conjugate was synthesized and characterized. It was radiolabeled with (68)Ga in ≥ 95% radiolabeling yields. In vitro cell binding studies showed a maximum cell uptake of 1.7±0.4% per million KB cells which was completely blocked on addition of cold folic acid showing specificity towards the FRs. However, further studies in tumor xenografts are warranted in order to assess the potential of (68)Ga-folic acid complex for imaging tumors over-expressing FRs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Ageing results in decline of normal functioning in all organ systems including skin. This predisposes the elderly persons to develop various skin ailments. A thorough knowledge of different diseases prevalent in this population in different geographic regions help the health care providers in better health care policy making., Aim: This study was planned to know the common dermatological diseases prevalent in Uttarakhand region of India., Materials and Methods: Hospital out patients records maintained in Department of Dermatology, Venereology & Leprosy were analysed and information regarding age, sex and diagnosis of patients were recorded. Descriptive statistics for prevalence of skin diseases in patients presenting to hospital were calculated., Results: Out of the total 29,422 patients seen in dermatology department from August 2012 to 2014, 4.7% (1,380) were aged 60 years and above. Male to female ratio was 2:1. Erythemato-squamous disorders taken collectively constituted the major skin disorder seen in 38.9% patients. This was followed by infections and infestations (29.9%), senile pruritus (9.0%) and age related skin changes (3.7%). Benign neoplasms were seen in 1.1% patients followed by cutaneous malignancies in 0.8% and precancerous lesions in 0.4%. Fungal infections were the most common infections seen in 18% patients., Conclusion: This study strengthens the opinion that infections, senile pruritus and eczema-dermatitis are the major dermatological disorders in elderly population.

Objective: To study intra-gastric pressures in neonates receiving bubble continuous positive airway pressure (BCPAP) by nasopharyngeal prong., Methods: Twenty seven neonates were recruited for the study. BCPAP pressure of 6 cm water was used in all the neonates. A pressure sensor attached to orogastric tube, measured the intra-gastric pressure prior to starting BCPAP and again between 30 and 90 min of BCPAP. The clinical variables like Downe's score, oxygen saturation, venous blood gas pH, pCO(2) and abdominal girth were recorded alongside with pressure readings., Results: BCPAP resulted in improvement (p < 0.05) in parameters of respiratory distress such as Downe's score (DS), oxygen saturation (SpO(2)) and venous blood gas parameters (pH, pCO(2)). There was no statistical significant increase in intra-gastric pressures (p = 0.834). There were no gastrointestinal complications; abdominal distention, necrotising enterocolitis or gastric perforation during the study., Conclusions: Nasopharyngeal BCPAP at 6 cm of water pressure is an effective modality of treating babies with respiratory distress and the present study shows that it is not associated with a significant rise in intra-gastric pressures.