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We and others have shown that [ 18 F]-Flortaucipir, the most validated tau PET tracer thus far, binds with strong affinity to tau aggregates in Alzheimer's (AD) but has relatively low affinity for tau aggregates in non-AD tauopathies and exhibits off-target binding to neuromelanin- and melanin-containing cells, and to hemorrhages. Several second-generation tau tracers have been subsequently developed. [ 18 F]-MK-6240 and [ 18 F]-PI-2620 are the two that have garnered most attention. Our recent data indicated that the binding pattern of [ 18 F]-MK-6240 closely parallels that of [ 18 F]-Flortaucipir. The present study aimed at the direct comparison of the autoradiographic binding properties and off-target profile of [ 18 F]-Flortaucipir, [ 18 F]-MK-6240 and [ 18 F]-PI-2620 in human tissue specimens, and their potential binding to monoamine oxidases (MAO). Phosphor-screen and high resolution autoradiographic patterns of the three tracers were studied in the same postmortem tissue material from AD and non-AD tauopathies, cerebral amyloid angiopathy, synucleopathies, transactive response DNA-binding protein 43 (TDP-43)-frontotemporal lobe degeneration and controls. Our results show that the three tracers show nearly identical autoradiographic binding profiles. They all strongly bind to neurofibrillary tangles in AD but do not seem to bind to a significant extent to tau aggregates in non-AD tauopathies pointing to their limited utility for the in vivo detection of non-AD tau lesions. None of them binds to lesions containing β-amyloid, α-synuclein or TDP-43 but they all show strong off-target binding to neuromelanin and melanin-containing cells, as well as weaker binding to areas of hemorrhage. The autoradiographic binding signals of the three tracers are only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline suggesting that MAO enzymes do not appear to be a significant binding target of any of them. These findings provide relevant insights for the correct interpretation of the in vivo behavior of these three tau PET tracers., (© 2024. The Author(s).)

The relationship between insulin resistance and coronary artery disease (CAD) is a crucial study area in understanding the complex connection between metabolic dysregulation and cardiovascular morbidity. This scholarly investigation examines the intricate relationship between insulin resistance, a key characteristic of metabolic syndrome, and CAD development. The goal is to understand the detailed molecular and physiological connections that underlie the dangerous connection between the endocrine and cardiac systems. The recognition of insulin resistance as a key player in cardiovascular disease highlights the need to study the complex relationships between insulin signaling pathways and the development of atherosclerosis. This research analyzes the molecular processes by which insulin resistance leads to disruptions in lipid metabolism, inflammatory reactions, and malfunction of the blood vessel's inner lining. These processes create an environment that promotes the development and advancement of CAD. As we begin this scientific exploration, it becomes clear that insulin resistance acts as a metabolic indicator and a potent mediator of endothelial dysfunction, oxidative stress, and systemic inflammation. The complex interaction between insulin-sensitive tissues and the vascular endothelium plays a crucial role in defining the pathophysiological landscape of CAD. Furthermore, this discussion highlights the mutual interaction between the endocrine and cardiac systems, where CAD produced by myocardial ischemia worsens insulin resistance through complex molecular pathways. Discovering new therapeutic targets that disrupt the harmful cycle between insulin resistance and the development of CAD shows potential for creating specific therapies to reduce cardiovascular risk in people with insulin resistance. This study aims to clarify the complexities of the connection between the endocrine system and the heart, establishing the basis for a thorough comprehension of how insulin resistance contributes to the development and advancement of CAD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ashraf et al.)

Recent observations of wingless animals, including jumping nematodes, springtails, insects, and wingless vertebrates like geckos, snakes, and salamanders, have shown that their adaptations and body morphing are essential for rapid self-righting and controlled landing. These skills can reduce the risk of physical damage during collision, minimize recoil during landing, and allow for a quick escape response to minimize predation risk. The size, mass distribution, and speed of an animal determine its self-righting method, with larger animals depending on the conservation of angular momentum and smaller animals primarily using aerodynamic forces. Many animals falling through the air, from nematodes to salamanders, adopt a skydiving posture while descending. Similarly, plant seeds such as dandelions and samaras are able to turn upright in mid-air using aerodynamic forces and produce high decelerations. These aerial capabilities allow for a wide dispersal range, low-impact collisions, and effective landing and settling. Recently, small robots that can right themselves for controlled landings have been designed based on principles of aerial maneuvering in animals. Further research into the effects of unsteady flows on self-righting and landing in small arthropods, particularly those exhibiting explosive catapulting, could reveal how morphological features, flow dynamics, and physical mechanisms contribute to effective mid-air control. More broadly, studying apterygote (wingless insects) landing could also provide insight into the origin of insect flight. These research efforts have the potential to lead to the bio-inspired design of aerial micro-vehicles, sports projectiles, parachutes, and impulsive robots that can land upright in unsteady flow conditions., (© 2023 IOP Publishing Ltd.)

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes the complicated disease COVID-19. Clinicians are continuously facing huge problems in the treatment of patients, as COVID-19-specific drugs are not available, hence the principle of drug repurposing serves as a one-and-only hope. Globally, the repurposing of many drugs is underway; few of them are already approved by the regulatory bodies for their clinical use and most of them are in different phases of clinical trials. Here in this review, our main aim is to discuss in detail the up-to-date information on the target-based pharmacological classification of repurposed drugs, the potential mechanism of actions, and the current clinical trial status of various drugs which are under repurposing since early 2020. At last, we briefly proposed the probable pharmacological and therapeutic drug targets that may be preferred as a futuristic drug discovery approach in the development of effective medicines., (© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Helicobacter pylori infection is seropositive in ~50% of people globally. Therefore, this study was conducted to evaluate its prevalence in dyspepsia patients., Methods: A cross-sectional study was conducted at Jinnah Postgraduate Medical Centre (JPMC) from January to June 2022 to find out the prevalence and risk factors of H. pylori in dyspepsia patients. A prevalidated questionnaire was used to collect the data from 180 patients. This study adheres to the principles outlined in the Helsinki Declaration. The χ 2 -test was applied, and the odds ratio and 95% CI were calculated to find the association of H. pylori with the risk factors., Results: A total of 180 patients were enrolled in this study, of whom, 73 (40.6%) patients were male and 107 (59.4%) were female. In seropositive H. pylori patients, 80 (60.6%) patients had nausea or vomiting, 110 (83.3%) patients were found to have flatulence, 128 (97.7%) patients were experiencing frequent burping, and 114 (86.4%) patients were having epigastric pain. The household member greater than 4, smoking, rural area residence, NSAIDs consumption, BMI greater than 25, O+ blood group, and Rhesus positive status were significantly associated with H. pylori with a P value of less than 0.05., Conclusion: This study concludes that the prevalence of H. pylori in our population is high, and the risk factors identified are lower class, BMI greater than 25, smoking, O+ blood group, NSAID consumption, rural area residence, household member greater than 4, Rhesus positive status, and the symptoms of nausea or vomiting, frequent burping, epigastric pain, and flatulence. Patients with an increased number of risk factors should be taken into consideration for an appropriate checkup., Competing Interests: No conflicts of interest declared.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Climate change and its impact on agriculture productivity vary among crops and regions. The southeastern United States (SE-US) is agro-ecologically diversified, economically dependent on agriculture, and mostly overlooked by agroclimatic researchers. The objective of this study was to compute the effect of climatic variables; daily maximum temperature (T max ), daily minimum temperature (T min ), and rainfall on the yield of major cereal crops i.e., corn (Zea mays L.), rice (Oryza sativa L.), and wheat (Triticum aestivum L.) in SE-US. A fixed-effect model (panel data approach) was used by applying the production function on panel data from 1980 to 2020 from 11 SE-US states. An asymmetrical warming pattern was observed, where nocturnal warming was 105.90%, 106.30%, and 32.14%, higher than the diurnal warming during corn, rice, and wheat growing seasons, respectively. Additionally, a shift in rainfall was noticed ranging from 19.2 to 37.2 mm over different growing seasons. Rainfall significantly reduced wheat yield, while, it had no effect on corn and rice yields. The T max and T min had no significant effect on wheat yield. A 1 °C rise in T max significantly decreased corn (- 34%) and rice (- 8.30%) yield which was offset by a 1 °C increase in T min increasing corn (47%) and rice (22.40%) yield. Conclusively, overall temperature change of 1 °C in the SE-US significantly improved corn yield by 13%, rice yield by 14.10%, and had no effect on wheat yield., (© 2022. The Author(s).)

In acute respiratory failure due to severe coronavirus disease 2019 (COVID-19) pneumonia, mechanical ventilation remains challenging and may result in high mortality. The use of noninvasive ventilation (NIV) may delay required invasive ventilation, increase adverse outcomes, and have a potential aerosol risk to caregivers. Data of 30 patients were collected from patient files and analyzed. Twenty-one (70%) patients were weaned successfully after helmet-NIV support (NIV success group), and invasive mechanical ventilation was required in 9 (30%) patients (NIV failure group) of which 8 (26.7%) patients died. In NIV success vs failure patients, the mean baseline PaO 2 /FiO 2 ratio (PFR) (147.2 ± 57.9 vs 156.8 ± 59.0 mm Hg; p = 0.683) and PFR before initiation of helmet (132.3 ± 46.9 vs 121.6 ± 32.7 mm Hg; p = 0.541) were comparable. The NIV success group demonstrated a progressive improvement in PFR in comparison with the failure group at 2 hours (158.8 ± 56.1 vs 118.7 ± 40.7 mm Hg; p = 0.063) and 24 hours (PFR-24) (204.4 ± 94.3 vs 121.3 ± 32.6; p = 0.016). As predictor variables, PFR-24 and change (delta) in PFR at 24 hours from baseline or helmet initiation (dPFR-24) were significantly associated with NIV success in univariate analysis but similar significance could not be reflected in multivariate analysis perhaps due to a small sample size of the study. The PFR-24 cutoff of 161 mm Hg and dPFR-24 cutoff of -1.44 mm Hg discriminate NIV success and failure groups with the area under curve (confidence interval) of 0.78 (0.62-0.95); p = 0.015 and 0.74 (0.55-0.93); p = 0.039, respectively. Helmet interface NIV may be a safe and effective tool for the management of patients with severe COVID-19 pneumonia with acute respiratory failure. More studies are needed to further evaluate the role of helmet NIV especially in patients with initial PFR <150 mm Hg to define PFR/dPFR cutoff at the earliest time point for prediction of helmet-NIV success. How to cite this article Jha OK, Kumar S, Mehra S, Sircar M, Gupta R . Helmet NIV in Acute Hypoxemic Respiratory Failure due to COVID-19: Change in PaO 2 /FiO 2 Ratio a Predictor of Success. Indian J Crit Care Med 2021;25(10):1137-1146., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.)

The carboxy-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin ligase and co-chaperone belonging to Ubox family that plays a crucial role in the maintenance of cellular homeostasis by switching the equilibrium of the folding-refolding mechanism towards the proteasomal or lysosomal degradation pathway. It links molecular chaperones viz . HSC70, HSP70 and HSP90 with ubiquitin proteasome system (UPS), acting as a quality control system. CHIP contains charged domain in between N-terminal tetratricopeptide repeat (TPR) and C-terminal Ubox domain. TPR domain interacts with the aberrant client proteins via chaperones while Ubox domain facilitates the ubiquitin transfer to the client proteins for ubiquitination. Thus, CHIP is a classic molecule that executes ubiquitination for degradation of client proteins. Further, CHIP has been found to be indulged in cellular differentiation, proliferation, metastasis and tumorigenesis. Additionally, CHIP can play its dual role as a tumor suppressor as well as an oncogene in numerous malignancies, thus acting as a double agent. Here, in this review, we have reported almost all substrates of CHIP established till date and classified them according to the hallmarks of cancer. In addition, we discussed about its architectural alignment, tissue specific expression, sub-cellular localization, folding-refolding mechanisms of client proteins, E4 ligase activity, normal physiological roles, as well as involvement in various diseases and tumor biology. Further, we aim to discuss its importance in HSP90 inhibitors mediated cancer therapy. Thus, this report concludes that CHIP may be a promising and worthy drug target towards pharmaceutical industry for drug development., (© 2021 Chongqing Medical University. Production and hosting by Elsevier B.V.)

Background: TDP-43 proteinopathy is a pathological hallmark of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). So far, there is no therapy available for these neurodegenerative diseases. In addition, the impact of TDP-43 proteinopathy on neuronal translational profile also remains unknown., Methods: Biochemical, immunohistology and assay-based studies were done with cell cultures and transgenic mice models. We also used Ribotag with microarray and proteomic analysis to determine the neuronal translational profile in the mice model of ALS/FTD., Results: Here, we report that oral administration of a novel analog (IMS-088) of withaferin-A, an antagonist of nuclear factor kappa-B (NF-ĸB) essential modulator (NEMO), induced autophagy and reduced TDP-43 proteinopathy in the brain and spinal cord of transgenic mice expressing human TDP-43 mutants, models of ALS/FTD. Treatment with IMS-088 ameliorated cognitive impairment, reduced gliosis in the brain of ALS/FTD mouse models. With the Ribotrap method, we investigated the impact of TDP-43 proteinopathy and IMS-088 treatment on the translation profile of neurons of one-year old hTDP-43 A315T mice. TDP-43 proteinopathy caused translational dysregulation of specific mRNAs including translational suppression of neurofilament mRNAs resulting in 3 to 4-fold decrease in levels type IV neurofilament proteins. Oral administration of IMS-088 rescued the translational defects associated with TDP-43 proteinopathy and restored the synthesis of neurofilament proteins, which are essential for axon integrity and synaptic function., Conclusions: Our study revealed that induction of autophagy reduces TDP-43 pathology and ameliorates the translational defect seen in mice models of ALS/FTD. Based on these results, we suggest IMS-088 and perhaps other inducers of autophagy should be considered as potential therapeutics for neurodegenerative disorders with TDP-43 proteinopathies.

Withaferin-A, an active withanolide derived from the medicinal herbal plant Withania somnifera induces autophagy, reduces TDP-43 proteinopathy, and improves cognitive function in transgenic mice expressing mutant TDP-43 modelling FTLD. TDP-43 is a nuclear DNA/RNA-binding protein with cellular functions in RNA transcription and splicing. Abnormal cytoplasmic aggregates of TDP-43 occur in several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and limbic-predominant age-related TDP-43 encephalopathy (LATE). To date, no effective treatment is available for TDP-43 proteinopathies. Here, we tested the effects of withaferin-A (WFA), an active withanolide extracted from the medicinal herbal plant Withania somnifera, in a transgenic mouse model of FTLD expressing a genomic fragment encoding mutant TDP-43 G348C . WFA treatment ameliorated the cognitive performance of the TDP-43 G348C mice, and it reduced NF-κB activity and neuroinflammation in the brain. WFA alleviated TDP-43 pathology while it boosted the levels of the autophagic marker LC3BII in the brain. These data suggest that WFA and perhaps other autophagy inducers should be considered as potential therapy for neurodegenerative diseases with TDP-43 pathology.

Hypothesis: Mixing of a chemical trigger of lower surface tension into a microdroplet with relatively higher surface tension can cause a rapid spreading of the droplet on a liquid-sublayer to form a host of metastable liquid morphologies such as sheets, toroids, threads, or droplets. Subsequently, such metastable fluidic objects break into a collection of droplets to form microemulsions., Experiments: Introduction of surfactant loaded water or long-chain alcohols into an oleic acid microdroplet stimulate a rapid spreading of the same on a water sublayer, which helps in the formation of a metastable liquid sheet connected to a liquid toroid. Much like slipping films, the liquid sheet dewets the water underlayer through the formation of holes before they grow and coalesce to form liquid ribbons. While such liquid structures eventually break into an array of microdroplets, the liquid toroid expands before undergoing a Plateau-Rayleigh instability to form microdroplets., Findings: A single step self-organization process in which a chemical trigger can convert a microdroplet into a liquid-toroid on a water surface, in absence of any rotational influence. A symmetric to asymmetric transition in toroid morphology is observed due to the changeover of laminar to turbulent flow regimes with the reduction in viscosity of fluid-sublayer or variation in chemical triggers. The toroid cross-section and droplet spacing after the toroid breakup follow a length scale evaluated from a linear stability analysis., 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 © 2020 Elsevier Inc. All rights reserved.)

Native buckwheat starch was extracted and modified by heat-moisture treatment (HMT) with different treatment time (15, 30 and 45 min) to investigate its effect on physicochemical, morphological, functional properties, starch profile (rapidly digestible starch, RDS; slowly digestible starch, SDS and resistant starch, RS fractions) and expected glycemic index (eGI). Results revealed that with increasing time duration of HMT from 15 to 45 min, amylose content, pasting temperature and thermostability increased substantially whereas swelling power, solubility and viscosity parameters decreased. The SEM micrographs showed that HMT caused fissures in the granule and surface indentation. HMT-45 (starch treated for 45 min) had the lowest RDS content (29.33%) and the highest SDS (51.30%) and RS (8.21%) levels. The decreased hydrolysis rate, high amylose and RS content of HMT-45 resulted in a significant decrease in estimated glycemic index (eGI) values from 51.49% (Native) to 44.16% (HMT-45) thus indicating its role in prevention of non-insulin- dependent diabetes., (© Association of Food Scientists & Technologists (India) 2020.)

Effect of hydrothermal modifications (autoclaving, annealing and heat moisture treatment) on physico-chemical, rheological properties and in vitro digestibility of kithul starch was studied. Annealing and heat moisture treatment decreased swelling index, solubility and increased crystalline properties as compared with autoclaving. Autoclaving, annealing and heat moisture treatment caused significant morphological damages such as large holes and fissures on the kithul starch, in addition, granules changed from oval to donut shape. Heat moisture treatment formed higher number of agglomerated starch granules. Light transmittance decreased after hydrothermal modifications. Autoclaving and annealing increased the pasting viscosities (except break down viscosity) of kithul starch. A significant increase ( p  ≤ 0.05) in peak temperature, conclusion temperature and enthalpy was found in annealed and heat moisture treated kithul starches. The digestibility of kithul starch decreased with increasing resistant starch after annealing and heat moisture treatment. Autoclaved, annealed and heat moisture treated kithul starches exhibited higher value of storage modulus (G') and loss modulus (G″) than native kithul starch. It entail to higher firmness of modified starch gel. The current study showed that the remarkable changes formed by hydrothermal modifications increased the industrial acceptance of kithul starch., Competing Interests: Conflict of interestThere is no conflict of interest., (© Association of Food Scientists & Technologists (India) 2020.)

The study reveals effect of pre-treatments, i.e., partial drying (PD), partial drying + freezing (PDF) and freezing (F) on physico-chemical, structural and sensory quality of vacuum fried papaya chips (100 °C for 28 min at 13.33 kPa). Pre-treatments significantly ( p  < 0.05) influenced the quality parameters of vacuum fried papaya chips. Partial drying pre-treated sample showed significantly ( p  < 0.05) higher reduction in oil uptake, i.e., 19.61% ( d.b. ) besides retaining significantly ( p  < 0.05) higher total phenolics content (394.07 mg/100 g gallic acid equivalent) as compared to other samples. Ascorbic acid content was retained significantly ( p  < 0.05) high in untreated control samples (209.81 mg/100 g). Freezing pre-treatment was found better in retaining total flavonoids, total carotenoids and antioxidant activity. The SEM micrographs of papaya chips showed dense and shriveled structure due to partial drying pre-treatment, however, more porous structure was observed in freezing pre-treated sample as compared to control. Freezing pre-treated samples were also rated high on hedonic scale for their sensory parameters, i.e., colour, crispness, taste, mouth feel, appearance and overall acceptability, which were in agreement with instrumental CIE colour values, firmness and microstructural characteristics of samples. The percent moisture, fat, protein, total carbohydrate, and ash content of freezing pre-treated vacuum fried papaya chips was found to be 1.51 ± 0.13%, 23.68 ± 0.12%, 3.42 ± 0.14%, 67.64 ± 1.78% and 3.75 ± 0.08%, respectively., (© Association of Food Scientists & Technologists (India) 2020.)