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Introduction: Alzheimer pathology (AD) is characterized by the deposition of amyloid beta (Aβ) and chronic neuroinflammation, with the NLRP3 inflammasome playing a significant role. This study demonstrated that the OCD drug fluvoxamine maleate (FXN) can potently ameliorate AD pathology in 5XFAD mice by promoting autophagy-mediated clearance of Aβ and inhibiting the NLRP3 inflammasome. Methods: We used mice primary astrocytes to establish the mechanism of action of FXN against NLRP3 inflammasome by using various techniques like ELISA, Western blotting, confocal microscopy, Immunofluorescence, etc. The anti-AD activity of FXN was validated in transgenic 5XFAD mice following two months of treatment. This was followed by behavior analysis, examination of inflammatory and autophagy proteins and immunohistochemistry analysis for Aβ load in the hippocampi. Results: Our data showed that FXN, at a low concentration of 78 nM, induces autophagy to inhibit NF-κB and the NLRP3 inflammasome, apart from directly inhibiting NLRP3 inflammasome in primary astrocytes. FXN activated the PRKAA2 pathway through CAMKK2 signaling, leading to autophagy induction. It inhibited the ATP-mediated NLRP3 inflammasome activation by promoting the autophagic degradation of NF-κB, resulting in the downregulation of pro-IL-1β and NLRP3. The anti-NLRP3 inflammasome effect of FXN was reversed when autophagy was inhibited by either genetic knockdown of the PRKAA2 pathway or pharmacological inhibition with bafilomycin A1. Furthermore, FXN treatment led to improved AD pathology in 5XFAD mice, resulting in significant improvements in various behavioral parameters such as working memory and neuromuscular coordination, making their behavior more similar to that of wild-type animals. FXN improved behavior in 5XFAD mice by clearing the Aβ deposits from the hippocampi and significantly reducing multiple inflammatory proteins, including NF-κB, GFAP, IBA1, IL-1β, TNF-α, and IL-6, which are associated with NF-κB and NLRP3 inflammasome in the brain. Moreover, these changes were accompanied by increased expression of autophagic proteins. Discussion: Our data suggest that FXN ameliorates AD pathology, by simultaneously targeting two key pathological features: Aβ deposits and neuroinflammation. As an already approved drug, FXN holds potential as a candidate for human studies against AD. [ABSTRACT FROM AUTHOR]

Continuous power supply in an integrated electric system supplied by solar energy and battery storage can be optimally maintained with the use of diesel generators. This article discusses the optimum setting-point for isolated wind, photo-voltaic, diesel, and battery storage electric grid systems. Optimal energy supply for hybrid grid systems means that the load is sufficient for 24 h. This study aims to integrate the battery deprivation costs and the fuel price feature in the optimization model for the hybrid grid. In order to count charge–discharge cycles and measure battery deprivation, the genetic algorithm concept is utilized. To solve the target function, an ANN-based algorithm with genetic coefficients can also be used to optimize the power management system. In the objective function, a weight factor is proposed. Specific weight factor values are considered for simulation studies. On the algorithm actions, charging status, and its implications for the optimized expense of the hybrid grid, the weight factor effect is measured.

Neonatal period, which is the first 28 days of an infant’s life, is the most crucial and vulnerable period. A remarkable decline in mortality rates during neonatal period for the past two decades is due to the advances of obstetric practice in term of medical screening and surveillance and increased neonatal specialization. However, respiratory tract disorders, along with sepsis and other types of infection, are the major causes of neonatal morbidities and mortalities. Hence, this study is aimed to bridge these gaps and provide inputs to the program implementers to design necessary interventions that could contribute to the reduction of neonatal morbidity and mortality. Aims: To determine the clinical profile and neonatal outcome admitted to NICU in district hospital Objectives: 1. To determine the socio demographic factors associated with neonatal outcome 2. To determine the obstetric profile associated with neonatal outcome. Methods: This hospital based retrospective study was conducted in the NICU of Tumakuru district hospital from Jan to March 2023. Records of all the admitted neonates were reviewed. The details were collected based on a structured questionnaire prepared in English. This contained information regarding obstetric and antenatal care (ANC), gestational age at birth, birth weight, sex, APGAR score, age at admission, admission diagnosis, neonatal outcomes and other related details. The data collected was entered in Microsoft excel (MS Excel) and quantitative variables was analysed by mean and qualitative variable by proportion by epi in go 3.4.3. Chi square was used to find out the association between the neonatal outcome and other variables. P value <0.05 was considered significant. Results: A total of 120 neonates were admitted during the study period. 47 (39.1%) mothers of the neonates were aged 21-25years and followed by 34 (28.3%) mothers in the age of 26-30 years. Association between neonatal outcome and socio demographic components was not statistically significant but definitely outcome was better with the good socio demographic profile. Regarding ANC follow up, 119 (99.1%) mothers had attended at least one prenatal visit and majority 100 (80%) were having ANC check-up at government hospital. The most common causes of neonatal mortality were respiratory distress syndrome 4(3.33%), followed by low birth weight 4(3.33%), and preterm 3(2.5%). Conclusion: Inspite of improved technology and facilities available still the neonatal outcome is worst. These all are preventable causes of neonatal mortality and morbidities which has to be taken care bygiving due importance to its predictors. Maternal and environmental factors has to be taken care and dealt. [ABSTRACT FROM AUTHOR]

The Maldives tuna fishery landings in 2018 were 148, 000 t and accounted for nearly a quarter of the global pole-and-line tuna catch. This fishery partially relies on a network of 55 anchored fish aggregating devices (AFADs) deployed around the archipelago. About one-third of the total pole-and-line tuna catch is harvested at AFADs. Although the AFAD fishery has existed for 35 years, knowledge on the behaviour of tuna in the AFAD array is still limited, precluding the development of science-based fishery management. In this study, local ecological knowledge (LEK) of fishers was used to improve our understanding of tuna behaviour, through personal interviews of 54 pole-and-line fishers from different parts of the archipelago. Interview results suggest that during the northeast monsoon tuna are more abundant on the eastern side of the Maldives, while during the southwest monsoon they are more abundant on the western side of the Maldives. Most fishers believed that tuna tend to stay at the AFADs for 3 to 6 days and remain within 2 miles from the AFADs when they are associated. Fishers believe that strong currents is the main factor for tuna departure from AFADs, though high sea surface temperatures and stormy conditions were also thought to contribute to departures. Moderate currents are believed to be a favourable condition to form aggregations at the AFADs while other factors such as suitable temperature, prey and attractants enhance this aggregation. Fishers also believe that there are multiple schools segregated according to size and species at AFADs and that catchability is higher at dawn and in the late afternoon when the tuna occur shallower in the water column. This study is an important step towards engaging the Maldivian tuna fishers into a science-based fishery management.

The present work describes the s‐trichlorotriazine (TCT)‐mediated formation of highly functionalized ester‐based drugs, namely nafamostat mesylate and camostat mesylate. The TCT‐mediated activation of acids followed by the attack of a hydroxyl group (−OH group) resulted in the formation of ester. The high aqueous solubility of cyanuric acid eases the work‐up process and avoids repetitive washing process (better E‐factor). The present method also avoids using pyridine as a base, and instead of that, N‐methylmorpholine (NMM) was used for the coupling. Moreover, we have also demonstrated the synthesis of key intermediates namely, 4‐guanidinobenzoic acid and 6‐hydroxy‐2‐naphthimidamide from economical and readily available raw materials. The TCT‐mediated coupling provides many advantages in scalability, cost‐effectiveness and environmental friendly handling. [ABSTRACT FROM AUTHOR]

The Maldives tuna fishery landings in 2018 were 148, 000 t and accounted for nearly a quarter of the global pole-and-line tuna catch. This fishery partially relies on a network of 55 anchored fish aggregating devices (AFADs) deployed around the archipelago. About one-third of the total pole-and-line tuna catch is harvested at AFADs. Although the AFAD fishery has existed for 35 years, knowledge on the behaviour of tuna in the AFAD array is still limited, precluding the development of science-based fishery management. In this study, local ecological knowledge (LEK) of fishers was used to improve our understanding of tuna behaviour, through personal interviews of 54 pole-and-line fishers from different parts of the archipelago. Interview results suggest that during the northeast monsoon tuna are more abundant on the eastern side of the Maldives, while during the southwest monsoon they are more abundant on the western side of the Maldives. Most fishers believed that tuna tend to stay at the AFADs for 3 to 6 days and remain within 2 miles from the AFADs when they are associated. Fishers believe that strong currents is the main factor for tuna departure from AFADs, though high sea surface temperatures and stormy conditions were also thought to contribute to departures. Moderate currents are believed to be a favourable condition to form aggregations at the AFADs while other factors such as suitable temperature, prey and attractants enhance this aggregation. Fishers also believe that there are multiple schools segregated according to size and species at AFADs and that catchability is higher at dawn and in the late afternoon when the tuna occur shallower in the water column. This study is an important step towards engaging the Maldivian tuna fishers into a science-based fishery management. [ABSTRACT FROM AUTHOR]

Many viruses utilize the host endo-lysosomal network for infection. Tracing the endocytic itinerary of SARS-CoV-2 can provide insights into viral trafficking and aid in designing new therapeutic strategies. Here, we demonstrate that the receptor binding domain (RBD) of SARS-CoV-2 spike protein is internalized via the pH-dependent CLIC/GEEC (CG) endocytic pathway in human gastric-adenocarcinoma (AGS) cells expressing undetectable levels of ACE2. Ectopic expression of ACE2 (AGS-ACE2) results in RBD traffic via both CG and clathrin-mediated endocytosis. Endosomal acidification inhibitors like BafilomycinA1 and NH4Cl, which inhibit the CG pathway, reduce the uptake of RBD and impede Spike-pseudoviral infection in both AGS and AGS-ACE2 cells. The inhibition by BafilomycinA1 was found to be distinct from Chloroquine which neither affects RBD uptake nor alters endosomal pH, yet attenuates Spike-pseudovirus entry. By screening a subset of FDA-approved inhibitors for functionality similar to BafilomycinA1, we identified Niclosamide as a SARS-CoV-2 entry inhibitor. Further validation using a clinical isolate of SARS-CoV-2 in AGS-ACE2 and Vero cells confirmed its antiviral effect. We propose that Niclosamide, and other drugs which neutralize endosomal pH as well as inhibit the endocytic uptake, could provide broader applicability in subverting infection of viruses entering host cells via a pH-dependent endocytic pathway. Author summary: This study investigates the cellular mechanisms by which SARS-CoV-2 can gain entry into human cells. We find that the virus employs diverse endocytic processes to enter cells and the acidic environment within these endocytic compartments is essential for infection. Using these observations from first principles, we screened a small set of FDA-approved drugs which could potentially inhibit endosomal acidification and therefore prevent viral entry and infection. The routinely prescribed anti-helminthic drug, Niclosamide, was observed to have this capability. Our study proposes that drugs altering both endocytic entry as well as endosomal acidification can assist in the clinical management of viral infections. [ABSTRACT FROM AUTHOR]

Flagship species are used to leverage public support for conservation. The success of a flagship is potentially determined by its popularity and ability to foster conservation intentions among a target audience. When flagships come into conflict with people, however, it is likely that conservation intentions get negatively affected. By examining peoples' exposures to the Asian elephant—a global conservation flagship—this study sought to (a) identify exposures that enable conservation intentions and (b) test whether human-elephant conflict undermines them. Survey results showed that exposure to wild elephants negatively affected intentions to conserve elephants, while specific concern for the elephant and direct involvement in conservation activities led to positive intentions. These results suggest that the effective use of the Asian elephant as a flagship may be contingent on mitigating human-elephant conflict, for which engagement with concerned local actors and initiation of participatory conservation frameworks need to be considered. [ABSTRACT FROM AUTHOR]

Simple Summary: Like plants, animal-based remedies are being utilized traditionally in different cultures around the globe. We explored the traditional usage of wild animals by the local inhabitants in Ladakh area of Trans-Himalayan region, India, using questionnaires and interviews. Furthermore, associations between ethnozoological usage and animal species were also evaluated through multivariate ecological community analysis. The highest priority of local inhabitants was for food followed by medicinal usage. We documented therapeutic uses of 48% of the reported species. Among these Alectoris chukar (chukar), Cuon alpinus (Asiatic wild dog), Lepus oiostolus (hares), Marmota himalayana (marmots), Ovis aries vignei (Ladakh urial), Pantholops hodgsonii (Tibetan antelope), Procapra picticaudata (Tibetan gazelle), Pseudois nayaur (blue sheep), Tetraogallus himalayensis (Himalayan snow), Tetraogallus tibetanus (Tibetan snow cock), and Lutra lutra (common otter) were reported for the first time from this region and are being used for medicinal purpose. Our findings could be valuable as reference data for policymakers, researchers, land managers, common public, and the other stakeholders to develop logical and scientific approaches for sustainable use of faunal diversity in biodiversity hotspot regions. Zootherapy is accepted all around the globe not only in ancient cultures but different animal derived medicines are also part of the practice in the modern health care systems. The present study assessed the traditional ethnozoological usage of wild animals by local inhabitants in Ladakh region, India, and the reference data for scientific approaches for protection of faunal diversity in trans-Himalayas. The ethnozoological documentation of the animals in Ladakh was carried out through semistructured and close-ended questionnaire surveys and interviews. Multivariate ecological community analysis was used to elucidate the relationship between ethnozoological usage and animal species. Our results showed three animal usage clusters with 32% similarity. Moreover, the similarity in animal usage between digging tools, trophy, handle of tools, decoration, and matting, showed less than 32% of similarity. The highest priority of local people was for food followed by decoration and medicinal usage. The most frequently used animal parts were meat followed by fur and horn. Medicinal uses of 48% of the reported species, i.e., Alectoris chukar (chukar), Cuon alpinus (Asiatic wild dog), Lepus oiostolus (hares), Marmota himalayana (marmots), Ovis aries vignei (Ladakh urial), Pantholops hodgsonii (Tibetan antelope), Procapra picticaudata (Tibetan gazelle), Pseudois nayaur (blue sheep), Tetraogallus himalayensis (Himalayan snow), Tetraogallus tibetanus (Tibetan snow cock), and Lutra lutra (common otter) were reported for the first time from this region. Our study provides innovative information regarding the ethnozoological knowledge in the Ladakh region and reference data for policymakers, researchers, land managers, common public, and the other stakeholders to develop logical and scientific approaches for sustainable use of faunal diversity in hotspot regions like trans-Himalayas and other similar biodiversity-rich sites. [ABSTRACT FROM AUTHOR]

Herbal toothpowders are available in market in a wide varieties, which consist of various ingredients. In rural areas of the developing countries, they are still used for cleansing teeth. Erythema multiforme (EM) is an acute mucocutaneous disorder that is believed to be a sequel of a cytotoxic immunologic attack on keratinocytes which express non-self-antigens. A 31-year-old male who used herbal toothpowder for oral-hygiene maintenance presented with ulcers in mouth, encrustation on lips and target lesions on both hands, suggesting Erythema multiforme. An oral biopsy confirmed the diagnosis. To the best of our knowledge, there is no report of an association of herbal extracts and EM in the English literature. With this report, we present a rare new triggering factor of Erythema mutiforme, thus adding it to the endless list of aetiologies. [ABSTRACT FROM AUTHOR]

Zootherapy is accepted all around the globe not only in ancient cultures but different animal derived medicines are also part of the practice in the modern health care systems. The present study assessed the traditional ethnozoological usage of wild animals by local inhabitants in Ladakh region, India, and the reference data for scientific approaches for protection of faunal diversity in trans-Himalayas. The ethnozoological documentation of the animals in Ladakh was carried out through semistructured and close-ended questionnaire surveys and interviews. Multivariate ecological community analysis was used to elucidate the relationship between ethnozoological usage and animal species. Our results showed three animal usage clusters with 32% similarity. Moreover, the similarity in animal usage between digging tools, trophy, handle of tools, decoration, and matting, showed less than 32% of similarity. The highest priority of local people was for food followed by decoration and medicinal usage. The most frequently used animal parts were meat followed by fur and horn. Medicinal uses of 48% of the reported species, i.e., Alectoris chukar (chukar), Cuon alpinus (Asiatic wild dog), Lepus oiostolus (hares), Marmota himalayana (marmots), Ovis aries vignei (Ladakh urial), Pantholops hodgsonii (Tibetan antelope), Procapra picticaudata (Tibetan gazelle), Pseudois nayaur (blue sheep), Tetraogallus himalayensis (Himalayan snow), Tetraogallus tibetanus (Tibetan snow cock), and Lutra lutra (common otter) were reported for the first time from this region. Our study provides innovative information regarding the ethnozoological knowledge in the Ladakh region and reference data for policymakers, researchers, land managers, common public, and the other stakeholders to develop logical and scientific approaches for sustainable use of faunal diversity in hotspot regions like trans-Himalayas and other similar biodiversity-rich sites.

Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library. Ex vivo interferon-γ (IFN-γ) responses to JEV in healthy JEV-exposed donors were mostly CD8(+) and targeted nonstructural (NS) proteins, whereas IFN-γ responses in recovered JE patients were mostly CD4(+) and targeted structural proteins and the secreted protein NS1. Among patients, a high quality, polyfunctional CD4(+) T cell response was associated with complete recovery from JE. T cell responses from healthy donors showed a high degree of cross-reactivity to DENV that was less apparent in recovered JE patients despite equal exposure. These data reveal divergent functional CD4(+) and CD8(+) T cell responses linked to different clinical outcomes of JEV infection, associated with distinct targeting and broad flavivirus cross-reactivity including epitopes from DENV, West Nile, and Zika virus., (© 2016 Turtle et al.)

Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the "drivers" of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.