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Abstract Background The button mangrove (Conocarpus erectus L.) is regarded as a peripheral species within mangrove communities. This particular species has the ability to thrive in regions that are arid or semiarid, where there is limited availability of nutrients. This study provides evidence of the ecological dominance of Conocarpus erectus across various habitats, highlighting its adaptability and success throughout the country of Pakistan. We collected twelve populations from four distinct ecological regions, including artificial forest plantations, agricultural fields, roadsides, and wastelands, offering a comprehensive assessment of C. erectus adaptability across diverse environmental contexts. Results Forest plantation populations exhibited impressive shoot growth and moderate root lengths, with plants generally tall and well-weighted. Physiologically, they had moderate chlorophyll content and low carotenoid levels, with a balanced chlorophyll a/b ratio, indicating stable photosynthetic activity. Anatomically, these populations had thicker epidermal and cortical root layers but smaller vascular bundles and phloem regions. Stem and leaf structures were generally moderate in size, with thicker midribs and cortical layers in the leaves. Agricultural field populations showed robust shoot and root systems with balanced fresh and dry biomass. They exhibited high chlorophyll and carotenoid levels, indicating strong photosynthetic capacity. Root and stem anatomy revealed larger root areas, thicker cortex, and wide vascular bundles, reflecting enhanced structural development. Leaves from these populations had moderate midrib and cortical thickness, with larger stomatal areas, promoting efficient gas exchange. Roadside populations displayed deeper roots and reduced biomass production. These populations adapted to environmental stress through leaf expansion, with high leaf numbers and areas. Physiologically, populations had high chlorophyll content, with a high chlorophyll a/b ratio. Root and stem anatomy showed compact structures with smaller vascular bundles, indicating adaptation to harsher conditions. Leaf anatomy was moderate, with smaller vascular bundles and reduced water transport capacity. Wasteland populations exhibited poor growth and high shoot biomass despite small leaves. Physiologically, these populations had the highest total soluble protein and proline contents, reflecting stress adaptation. Anatomically, root and stem structures were variable, with some populations showing reduced cortical cell areas and smaller vascular bundles, indicating limited resource transport. Leaf structures had thicker lamina, thinner epidermal layers, and lower stomatal densities, reflecting adaptation to nutrient-poor soils. Conclusion This study reveals the adaptability and thriving potential of Conocarpus erectus across varied habitats, providing key insights into its resilience and survival strategies. Understanding these adaptive traits can support habitat restoration, conservation planning, and improve species management in diverse environmental conditions, especially in response to climate change and habitat degradation.

Abstract This study explored the drought resistance mechanisms of different populations of Sporobolus ioclados (Poaceae), locally known as “Sawri,” “Drabhri” and “Dhrbholi” native to Africa and the Indian Subcontinent. These populations were grown in conventional nursery practices at Khawaja Fareed Government College in Rahim Yar Khan, Pakistan, and subsequently subjected to four distinct levels of drought within carefully monitored experimental settings. The experiment was conducted in a two-factorial design involving populations and drought treatments and was repeated three times. The physiological and morphological responses of S. ioclados, including plant height, number of roots, root length, flag leaf area, stomatal features, proline concentration and nitrogen content, displayed significant variability in response to the imposed drought stress. Drought resulted in increases in proline concentration and nitrogen content. The number of roots decreased, while the length and width of the stomata increased in various populations. A combination of advanced statistical techniques, such as ANOVA, PCA, HCA, and DFA, provided a comprehensive understanding of the mechanism of plant adaptation and the extent of population diversity within the species. The Yazman and Nwab Wala populations exhibited the highest rates of photosynthesis and stomatal conductance, while S. ioclados demonstrated notable drought tolerance at the T4 level of drought stress. A negative correlation was found between proline levels, nitrogen contents, and photosynthesis, suggesting that proline has a protective role in drought. The diverse adaptation strategies indicated by S. ioclados populations have revealed the potential of this species for afforestation and climate change mitigation in dry environments.

Abstract Canola, a vital oilseed crop, is grown globally for food and biodiesel. With the enormous demand for growing various crops, the utilization of agriculturally marginal lands is emerging as an attractive alternative, including brackish-saline transitional lands. Salinity is a major abiotic stress limiting growth and productivity of most crops, and causing food insecurity. Salicylic acid (SA), a small-molecule phenolic compound, is an essential plant defense phytohormone that promotes immunity against pathogens. Recently, several studies have reported that SA was able to improve plant resilience to withstand high salinity. For this purpose, a pot experiment was carried out to ameliorate the negative effects of sodium chloride (NaCl) on canola plants through foliar application of SA. Two canola varieties Faisal (V1) and Super (V2) were assessed for their growth performance during exposure to high salinity i.e. 0 mM NaCl (control) and 200 mM NaCl. Three levels of SA (0, 10, and 20 mM) were applied through foliar spray. The experimental design used for this study was completely randomized design (CRD) with three replicates. The salt stress reduced the shoot and root fresh weights up to 50.3% and 47% respectively. In addition, foliar chlorophyll a and b contents decreased up to 61–65%. Meanwhile, SA treatment diminished the negative effects of salinity and enhanced the shoot fresh weight (49.5%), root dry weight (70%), chl. a (36%) and chl. b (67%). Plants treated with SA showed an increased levels of both enzymatic i.e. (superoxide dismutase (27%), peroxidase (16%) and catalase (34%)) and non-enzymatic antioxidants i.e. total soluble protein (20%), total soluble sugar (17%), total phenolic (22%) flavonoids (19%), anthocyanin (23%), and endogenous ascorbic acid (23%). Application of SA also increased the levels of osmolytes i.e. glycine betaine (31%) and total free proline (24%). Salinity increased the concentration of Na+ ions and concomitantly decreased the K+ and Ca2+ absorption in canola plants. Overall, the foliar treatments of SA were quite effective in reducing the negative effects of salinity. By comparing both varieties of canola, it was observed that variety V2 (Super) grew better than variety V1 (Faisal). Interestingly, 20 mM foliar application of SA proved to be effective in ameliorating the negative effects of high salinity in canola plants.

Abstract Pea (Pisum sativum L.), a globally cultivated leguminous crop valued for its nutritional and economic significance, faces a critical challenge of soil salinity, which significantly hampers crop growth and production worldwide. A pot experiment was carried out in the Botanical Garden, The Islamia University of Bahawalpur to alleviate the negative impacts of sodium chloride (NaCl) on pea through foliar application of ascorbic acid (AsA). Two pea varieties Meteor (V1) and Sarsabz (V2) were tested against salinity, i.e. 0 mM NaCl (Control) and 100 mM NaCl. Three levels of ascorbic acid 0 (Control), 5 and 10 mM were applied through foliar spray. The experimental design was completely randomized (CRD) with three replicates. Salt stress resulted in the suppression of growth, photosynthetic activity, and yield attributes in pea plants. However, the application of AsA treatments effectively alleviated these inhibitory effects. Under stress conditions, the application of AsA treatment led to a substantial increase in chlorophyll a (41.1%), chl. b (56.1%), total chl. contents (44.6%) and carotenoids (58.4%). Under salt stress, there was an increase in Na+ accumulation, lipid peroxidation, and the generation of reactive oxygen species (ROS). However, the application of AsA increased the contents of proline (26.9%), endogenous AsA (23.1%), total soluble sugars (17.1%), total phenolics (29.7%), and enzymatic antioxidants i.e. SOD (22.3%), POD (34.1%) and CAT (39%) in both varieties under stress. Salinity reduced the yield attributes while foliarly applied AsA increased the pod length (38.7%), number of pods per plant (40%) and 100 seed weight (45.2%). To sum up, the application of AsA alleviated salt-induced damage in pea plants by enhancing photosynthetic pigments, both enzymatic and non-enzymatic activities, maintaining ion homeostasis, and reducing excessive ROS accumulation through the limitation of lipid peroxidation. Overall, V2 (Sarsabz) performed better as compared to the V1 (Meteor).

Abstract Nickel (Ni) is known as a plant micronutrient and serves as a component of many significant enzymes, however, it can be extremely toxic to plants when present in excess concentration. Scientists are looking for natural compounds that can influence the development processes of plants. Therefore, it was decided to use proline as a protective agent against Ni toxicity. Proline (Pro) is a popularly known osmoprotectant to regulate the biomass and developmental processes of plants under a variety of environmental stresses, but its role in the modulation of Ni-induced toxicity in wheat is very little explored. This investigation indicated the role of exogenously applied proline (10 mM) on two wheat varieties (V1 = Punjab-11, V2 = Ghazi-11) exposed to Ni (100 mg/kg) stress. Proline mediated a positive rejoinder on morphological, photosynthetic indices, antioxidant enzymes, oxidative stress markers, ion uptake were analyzed with and without Ni stress. Proline alone and in combination with Ni improved the growth, photosynthetic performance, and antioxidant capacity of wheat plants. However, Ni application alone exhibited strong oxidative damage through increased H2O2 (V1 = 28.96, V2 = 55.20) accumulation, lipid peroxidation (V1 = 26.09, V2 = 38.26%), and reduced translocation of macronutrients from root to shoot. Application of Pro to Ni-stressed wheat plants enhanced actions of catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and total soluble protein (TSP) contents by 45.70, 44.06, 43.40, and 25.11% in V1, and 39.32, 46.46, 42.22, 55.29% in V2, compared to control plants. The upregulation of antioxidant enzymes, proline accumulation, and uptake of essential mineral ions has maintained the equilibrium of Ni in both wheat cultivars, indicating Ni detoxification. This trial insight into an awareness that foliar application of proline can be utilized as a potent biochemical method in mitigating Ni-induced stress and might serve as a strong remedial technique for the decontamination of polluted soil particularly with metals.

Thiourea (TU) is considered an essential and emerging biostimulant against the negative impacts of severe environmental stresses, including drought stress in plants. However, the knowledge about the foliar application of TU to mitigate drought stress in Linum usitatissimum L., has yet to be discovered. The present study was designed to assess the impact of foliar application of TU for its effects against drought stress in two flax cultivars. The study comprised two irrigation regimes [60% field capacity (FC) and the control (100% FC)], along with TU (0, 500, 1000 mg L−1) application at the vegetative stage. The findings indicated that drought stress reduced the shoot fresh weight (44.2%), shoot dry weight (67.5%), shoot length (41.5%), total chlorophyll (51.6%), and carotenoids (58.8%). Drought stress increased both cultivars' hydrogen peroxide (H2O2) and malondialdehyde (MDA). Foliar application of TU (1000 mg L−1) enhanced the growth and chlorophyll contents with or without drought stress. Under drought stress (60% FC), TU decreased MDA and H2O2 contents up to twofold. Moreover, TU application increased catalase (40%), peroxidase (13%), superoxide dismutase (30%), and total soluble protein contents (32.4%) differentially in both cultivars. Nevertheless, TU increased calcium (Ca2+) (42.8%), potassium (K+) (33.4%), and phosphorus (P) (72%) in shoots and decreased the elevated sodium (Na+) (28.2%) ions under drought stress. It is suggested that TU application (1000 mg L−1) enhances the growth potential of flax by enhancing photosynthetic pigment, nutrient uptake, and antioxidant enzymes under drought stress. Research outcomes, therefore, recommend that TU application can ameliorate drought-induced negative effects in L. usitatissimum L. seedlings, resulting in improved plant growth and mineral composition, as depicted by balanced primary and secondary metabolite accumulation.

Peritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Peritoneal colonization is impaired in PDAC cells with knockout (KO) of the cancer surface antigen mesothelin (MSLN) or by introducing Y318A mutation in MSLN to prevent binding to mucin-16 (MUC-16). MSLN has a membrane-bound form but is also shed to release soluble MSLN (sMSLN). Their individual roles in peritoneal metastasis are unknown. Here, a C-terminal truncated MSLN mutant (∆591) incapable of cell membrane insertion but proficient in secretion was engineered. Expression of ∆591 MSLN failed to rescue peritoneal metastasis in MSLN KO cells and inhibited peritoneal colonization when overexpressed in WT PDAC cells. Exposing PDAC cells to conditioned medium (CM) containing excess sMSLN impaired cancer cell clustering in vitro and in peritoneal fluid in vivo, while CM containing only Y318A sMSLN did not. These data demonstrate that interaction of membrane-bound MSLN with MUC-16 promotes cell clustering that is critical for efficient peritoneal metastasis. However, peritoneal colonization by MSLN KO cells was rescued by expression of ∆591 mutant MSLN bearing Y318A mutation, suggesting that sMSLN also has a MUC-16-independent role in peritoneal spread. Alterations in inflammatory signaling pathways occurred following KO cell exposure to CM containing sMSLN, and CM from cancer cells with intact peritoneal metastasis provoked increased KO cell secretion of IL-1α. While excess sMSLN inhibits cell clustering and peritoneal colonization, sMSLN may also promote PDAC peritoneal metastasis independent of MUC-16., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Sustainable water resource management in arid and water deficit regions requires optimal use of water resources due to competition among different water sectors. The purpose of this study is to model uncertainties in economic and hydro-climatic variables and parameters to optimize agricultural water management in irrigation system networks to have sustainable water use. The study focuses on mitigating water shortages in Iran's Varamin irrigation network through improved agricultural patterns and efficient water consumption. The impact of employing reclaimed wastewater containing nitrates instead of nitrogen fertilizers is also evaluated. A Fuzzy Multi-Objective Particle Swarm Optimization (F-MOPSO) is applied to maximize the net benefit, restore groundwater, and minimize nitrate leaching into the aquifer. The results demonstrate that replacing groundwater with reclaimed wastewater boosted net benefits by 21% while improving groundwater restoration by 82%. These results indicate that the developed fuzzy model can handle uncertainties in irrigation system networks with a sustainable water use perspective. This research can assist decision-makers within the water, agriculture, and the environment in finding sustainable water solutions and improving the current water consumption practices, considering environmental aspects of nitrogen leaching in other regions and highlighting the potential of the developed fuzzy model., 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 Elsevier Ltd. All rights reserved.)

Background: The button mangrove (Conocarpus erectus L.) is regarded as a peripheral species within mangrove communities. This particular species has the ability to thrive in regions that are arid or semiarid, where there is limited availability of nutrients. This study provides evidence of the ecological dominance of Conocarpus erectus across various habitats, highlighting its adaptability and success throughout the country of Pakistan. We collected twelve populations from four distinct ecological regions, including artificial forest plantations, agricultural fields, roadsides, and wastelands, offering a comprehensive assessment of C. erectus adaptability across diverse environmental contexts., Results: Forest plantation populations exhibited impressive shoot growth and moderate root lengths, with plants generally tall and well-weighted. Physiologically, they had moderate chlorophyll content and low carotenoid levels, with a balanced chlorophyll a/b ratio, indicating stable photosynthetic activity. Anatomically, these populations had thicker epidermal and cortical root layers but smaller vascular bundles and phloem regions. Stem and leaf structures were generally moderate in size, with thicker midribs and cortical layers in the leaves. Agricultural field populations showed robust shoot and root systems with balanced fresh and dry biomass. They exhibited high chlorophyll and carotenoid levels, indicating strong photosynthetic capacity. Root and stem anatomy revealed larger root areas, thicker cortex, and wide vascular bundles, reflecting enhanced structural development. Leaves from these populations had moderate midrib and cortical thickness, with larger stomatal areas, promoting efficient gas exchange. Roadside populations displayed deeper roots and reduced biomass production. These populations adapted to environmental stress through leaf expansion, with high leaf numbers and areas. Physiologically, populations had high chlorophyll content, with a high chlorophyll a/b ratio. Root and stem anatomy showed compact structures with smaller vascular bundles, indicating adaptation to harsher conditions. Leaf anatomy was moderate, with smaller vascular bundles and reduced water transport capacity. Wasteland populations exhibited poor growth and high shoot biomass despite small leaves. Physiologically, these populations had the highest total soluble protein and proline contents, reflecting stress adaptation. Anatomically, root and stem structures were variable, with some populations showing reduced cortical cell areas and smaller vascular bundles, indicating limited resource transport. Leaf structures had thicker lamina, thinner epidermal layers, and lower stomatal densities, reflecting adaptation to nutrient-poor soils., Conclusion: This study reveals the adaptability and thriving potential of Conocarpus erectus across varied habitats, providing key insights into its resilience and survival strategies. Understanding these adaptive traits can support habitat restoration, conservation planning, and improve species management in diverse environmental conditions, especially in response to climate change and habitat degradation., Competing Interests: Declarations. Consent to participate: All authors have equally contributed and participated in whole work. Competing interest: All authors declare that this research work is a result of independent studies and no conflict of interest exists related to this study., (© 2024. The Author(s).)

Globally, mental health problems in adolescents, alongside associated morbidity and mortality, have never been higher. Local living, working and environmental conditions, socio-economics, and intra-individual and inter-individual processes impact mental health. The risk of developing mental health problems is higher in certain areas, including East London. However, limited research explores East London adolescents' experiences of mental health. An in-depth and locally situated understanding of determinants shaping East London adolescents' happiness and sadness is needed. This study used Photovoice, a qualitative method within a community-based participatory research methodology, to generate photographic and textual data, which was analyzed using reflexive thematic analysis. This method allows participants to be part of knowledge production and authors to present the data. Our findings underscore the bidirectional interplay between environmental factors and adolescents' happiness and sadness. Gratitude for nature was described as increasing happiness: adolescents connected to nature to memories, appreciation, and leisure opportunities. Adolescents were concerned about the fragility of nature in response to urban development. The urban environment was perceived as imposing, inspiring, and offering therapeutic benefits blighted by pollution. Beautiful areas were described as paradisical and lacking, revealing urban development and economic productivity disparities. Our research documents the voices of an under-researched group, revealing novel insights while empowering adolescents as co-producers of mental health research. This study indicates participatory research is valuable for granting adolescents autonomy and addressing misrepresentation. The findings implicate multiple stakeholders, including "Health in All Policies." By deepening our understanding of adolescent mental health in East London, our study can be leveraged to bolster the effectiveness and relevance of interventions for East London adolescents., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Competing interests: None declared.

Introduction and Importance: Inflammatory myofibroblastic tumor IMT 1 is a rare neoplasm with diverse clinical presentations, needing histological confirmation for diagnosis. The tumor often mimics malignant conditions, making accurate diagnosis challenging., Case Presentation: We report a case of a 29-year-old male presenting with long standing recurrent abdominal pain, with more recent increasing frequency and associated weight loss. Imaging revealed a heterogenous soft tissue lesions causing mechanical small bowel obstruction, prompting surgical intervention. Histology analysis confirmed the diagnosis of IMT., Clinical Discussion: This case highlights the importance of considering IMT in the differential diagnosis of neoplastic mechanical small bowel obstruction, particularly in patients presenting with atypical symptoms and image findings. Despite its rarity, IMT should be considered, as it can present similarly to more common malignancies. Further research is warranted to unravel the pathogenesis and refine management strategies for this intriguing neoplasm., Conclusion: IMT is a rare and intriguing neoplasm that presents significant diagnostic challenge. This case emphasize the need for thorough histological evaluation to confirm rhe diagnosis and guide appropriate management strategies., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Kaposi sarcoma (KS) is an angioproliferative neoplasm that affects the skin and lymph nodes. Human herpesvirus-8 (HHV-8) triggers KS by infecting the endothelium and inducing angiogenesis through the production of vascular endothelial growth factors and cytokines. KS is characterized by purplish or hyperpigmented plaques involving the skin and mucous membranes, and visceral involvement is very rare. Pulmonary KS (PKS) is an exceedingly rare visceral manifestation of KS and has a poor prognosis. PKS often presents with cough, hemoptysis, pleuritic chest pain, fever, and weight loss. In this case series, we share our experience in diagnosing and treating two patients with PKS. We also provide a concise review of the epidemiology, signs and symptoms, diagnosis, and management of this rare condition., Competing Interests: None to declare., (Copyright 2024, Pelidis et al.)

The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to investigate the integration of cereal and germinated pseudocereals into set-type yogurt mimic, resulting in a novel and nutritious product. Four groups of yogurts mimic, namely CPY-1, CPY-2, CPY-3, and CPY-4, were prepared using different probiotic cultures, including L. acidophilus 21, L. plantarum 14, and L. rhamnosus 296 along with starter cultures. Notably, CPY-2 cultured with L. plantarum and L. rhamnosus and incubated for 12 h exhibited the most desirable attributes. The resulting yogurt demonstrated an acidity of 0.65%, pH of 4.37 and a probiotic count of 6.38 log CFU/mL. The logistic growth model fit revealed maximum growth rates (k, 1/h) and maximum bacterial counts (Nm log CFU/mL) for each CPY variant. The results revealed that CPY-2 significantly improved protein, dietary fiber, phenols and antioxidant capacities compared to the control. Scanning electron microscopy showed more structured and compact casein network in CPY-2, highlighting its superior textural characteristics. Overall, this study demonstrates the incorporation of cereal and germinated pseudocereals into set-type yogurt mimic offers health benefits through increased dietary fiber and β-glucan., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Urothelial carcinoma (UC) is prevalent, especially in elderly males. The high rate of recurrence, treatment regime, and follow-up monitoring make UC a global health and economic burden. Arsenic is a ubiquitous toxicant that can be found in drinking water, and it is known that exposure to arsenic is associated with UC development. Around 25% of diagnosed UC cases are muscle-invasive (MIUC) which have poor prognosis and develop chemoresistance, especially if tumors are associated with squamous differentiation (SD). The immortalized UROtsa cell line is derived from normal human urothelium and our lab has malignantly transformed these cells using arsenite (As 3+ ). These cells represent a basal subtype model of MIUC and the tumors derived from the As 3+ -transformed cells histologically and molecularly resemble clinical cases of the basal subtype of MIUC that have focal areas SD and expression of the basal keratins (KRT1, 5, 6, 14, and 16). Our previous data demonstrate that KRT6 protein expression correlates to areas of SD within the tumors. For this study, we performed a lentiviral knockdown of KRT6 in As 3+ -transformed UROtsa cells to evaluate the effects on morphology, gene/protein expression, growth, colony formation, and cisplatin sensitivity. The knockdown of KRT6 resulted in decreased expression of the basal keratins, decreased growth, decreased colony formation, and increased sensitivity to cisplatin, the standard treatment for MIUC. The results of this study suggest that KRT6 plays a role in UC cell growth and is an exploitable target to increase cisplatin sensitivity for MIUC tumors that may have developed resistance to cisplatin treatment.

Phytoconstituent based therapies have the potential to reduce the adverse effects and enhance overall patient compliance for different diseased conditions. Embelin (EMB) is a natural compound extracted from Embelia ribes that has demonstrated high therapeutic potential, particularly as anti-inflammatory and anticancer therapeutic applications. However, its poor water solubility and low oral bioavailability limitations make it challenging to use in biomedical applications. Nanostructure-based novel formulations have shown the potential to improve physicochemical and biological characteristics of active pharmaceutical ingredients obtained from plants. Different nanoformulations that have been utilized to encapsulate/entrap EMB for various therapeutic applications are nanoliposomes, nanostructured lipid carriers, niosomes, polymeric nanoparticles, nanosuspensions, phytosomes, self nanoemulsifying drug delivery system, silver nanoparticles, microparticles, solid lipid nanoparticle, gold nanoparticles and nanomicelles. The common methods reported for the preparation of EMB nanoformulations are thin film hydration, nanoprecipitation, ethanol injection, emulsification followed by sonication. The size of nanoformulations ranged in between 50 and 345 nm. In this review, the mentioned EMB loaded nanocarriers are methodically discussed for size, shape, drug entrapment, zeta potential, in vitro release & permeation and in vivo studies. Potential of EMB with other drugs (dual drug approach) incorporated in nanocarriers are also discussed (physicochemical and preclinical characteristics). Patents related to EMB nanoformulations are also presented which showed the clinical translation of this bioactive for future utilization in different indications., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: Massachusetts was the first to implement a state-wide menthol cigarette sales restriction in the USA. Following its implementation in June 2020, evidence showed declines in cigarette sales in Massachusetts; however, changes in nicotine replacement therapy (NRT) product sales are unknown., Methods: This cohort study analysed NRT products sold by US-based retailers available in 26 states from the Nielsen Retail Scanner Data. Outcomes were state-level 4-week aggregate sales of gum, lozenge and patch NRT products converted into pieces per 1000 adults (aged ≥18 years) who smoke cigarettes based on smoking rates from the Behavioral Risk Factor Surveillance System and corresponding population from the US Census Bureau. We used a difference-in-differences method to compare changes in NRT product sales in Massachusetts before (1 January 2017 to 13 June 2020) and after (14 June 2020 to 4 December 2021) the policy with sales in 25 states., Results: The analysis included 1664 observations for each NRT product, with 1170 from before and 494 from after the policy change. The 4-week NRT product sales per 1000 adults who smoke cigarettes in Massachusetts compared with the comparison states increased for gums by 643.11 (95% CI 365.33 to 920.89; p<0.001) pieces or 12.9% and for lozenges by 436.97 (95% CI 292.88 to 581.06; p<0.001) pieces or 17.9% but no statistically significant change in patches after implementing the policy., Conclusion: The increases in sales of gum and lozenge NRT products in Massachusetts after implementing the policy suggest that a nationwide ban on menthol cigarettes can increase NRT product use; therefore, interventions are needed to strengthen cessation support for adults who smoke cigarettes but intend to quit., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Cannabis in the USA is transitioning from a nationwide illegal status to liberalisation for medicinal or recreational use across different jurisdictions. As the acceptability and accessibility of cannabis continue to grow, updated knowledge on the cancer risk from recreational cannabis use is necessary to inform recommendations by public health organisations, policy makers, and clinical practitioners. We reviewed the evidence to date. Our umbrella review of current global epidemiological evidence reveals that links between cannabis exposure and cancer risk are more suggestive than conclusive. The cancer type most closely linked to cannabis use is non-seminoma testicular cancer. However, evidence is emerging of an increased risk of other types of cancer (eg, lung squamous cell carcinoma, head and neck squamous cell carcinoma, and oral, breast, liver, cervical, laryngeal, pancreatic, thyroid, and childhood cancer), underscoring the potential importance of incorporating prevention and cessation of cannabis use in cancer prevention efforts. Our review also identified the need for replication of previous studies for additional epidemiological investigations that use rigorous study designs, and data collection protocols free from the biases of major confounders, misclassification, and measurement error in assessing cannabis exposure. Research on the long-term health and economic consequences of all cannabis products (both medical and recreational) are also needed. Currently, the insufficient evidence on the health risks of cannabis use reduces the ability of policy makers, health-care professionals, and individuals to make informed decisions about cannabis use and could expose the public to a potentially serious health risk., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

This study explored the drought resistance mechanisms of different populations of Sporobolus ioclados (Poaceae), locally known as "Sawri," "Drabhri" and "Dhrbholi" native to Africa and the Indian Subcontinent. These populations were grown in conventional nursery practices at Khawaja Fareed Government College in Rahim Yar Khan, Pakistan, and subsequently subjected to four distinct levels of drought within carefully monitored experimental settings. The experiment was conducted in a two-factorial design involving populations and drought treatments and was repeated three times. The physiological and morphological responses of S. ioclados, including plant height, number of roots, root length, flag leaf area, stomatal features, proline concentration and nitrogen content, displayed significant variability in response to the imposed drought stress. Drought resulted in increases in proline concentration and nitrogen content. The number of roots decreased, while the length and width of the stomata increased in various populations. A combination of advanced statistical techniques, such as ANOVA, PCA, HCA, and DFA, provided a comprehensive understanding of the mechanism of plant adaptation and the extent of population diversity within the species. The Yazman and Nwab Wala populations exhibited the highest rates of photosynthesis and stomatal conductance, while S. ioclados demonstrated notable drought tolerance at the T4 level of drought stress. A negative correlation was found between proline levels, nitrogen contents, and photosynthesis, suggesting that proline has a protective role in drought. The diverse adaptation strategies indicated by S. ioclados populations have revealed the potential of this species for afforestation and climate change mitigation in dry environments., (© 2024. The Author(s).)

Background: Racial and ethnic disparities have been reported for HCC prognosis, although few studies fully account for clinically important factors and social determinants of health, including neighborhood socioeconomic status., Methods: We conducted a retrospective multicenter cohort study of patients newly diagnosed with HCC from January 2010 through August 2018 at 4 large health systems in the United States. We used multivariable logistic regression and cause-specific Cox proportional hazard models to identify factors associated with early-stage HCC presentation and overall survival., Results: Of 2263 patients with HCC (37.6% non-Hispanic White, 23.5% non-Hispanic Black, 32.6% Hispanic, and 6.4% Asian/other), 42.0% of patients presented at an early stage (Barcelona Clinic Liver Cancer stage 0/A). In fully adjusted models, there were persistent Black-White disparities in early-stage presentation (OR: 0.63, 95% CI: 0.45-0.89) but not Hispanic-White disparities (OR: 0.93, 95% CI: 0.70-1.24). Median survival was 16.2 (IQR: 5.8-36.8) months for White patients compared to 15.7 (IQR: 4.6-34.4) months for Hispanic, 10.0 (IQR: 2.9-29.0) months for Black, and 9.5 (IQR: 3.4-31.9) months for Asian/other patients. Black-White disparities in survival persisted after adjusting for individual demographics and clinical factors (HR: 1.30, 95% CI: 1.09-1.53) but were no longer observed after adding HCC stage and treatment (HR: 1.05, 95% CI: 0.88-1.24), or in fully adjusted models (HR: 0.97, 95% CI: 0.79-1.18). In fully adjusted models, Hispanic-White (HR: 0.87, 95% CI: 0.73-1.03) and Asian/other-White (HR: 0.85, 95% CI: 0.63-1.15) differences in survival were not statistically significant, although patients in high-SES neighborhoods had lower mortality (HR: 0.69, 95% CI: 0.48-0.99)., Conclusions: In a multicenter cohort of patients with HCC, racial and ethnic differences in HCC prognosis were explained in part by differences in tumor stage at diagnosis and neighborhood SES. These data inform targets to intervene and reduce disparities., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Health professionals are at a higher risk of developing WMSD due to the nature of their work. Ergonomic awareness and practice promote workers' general well-being and safety in the workplace., Aim: Assess the ergonomic awareness and practice among healthcare workers in the UAE, its relationship with demographic variables and determine the prevalence of musculoskeletal disorders (MSDs) in this population., Method: This was a cross-sectional study among 307 healthcare workers from hospitals in Dubai, Ajman, and Sharjah in the UAE. A self-administered online questionnaire was used for data collection. Chi-square tests were used to assess associations between variables., Results: In the present study, the majority were female (77.4%). Concerning the nationalities, non-EMR (71.4%) and EMR (28.6%). The majority fell within the age group of 30-39 (39%). Regarding work experience, 58% had over ten years of experience. Results showed that 89.3% had good ergonomic awareness, while 63.5% demonstrated good ergonomic practices. Musculoskeletal Disorders (MSDs) were reported by 89.6% of participants, with the most common areas of pain being the lower back, neck, and shoulders. Education level was significantly associated with ergonomic awareness (p < 0.05). Age (P < 0.05) and years of experience (P < 0.01) were significantly associated with ergonomic practice. A significant association was observed between MSD and ergonomic awareness (P < 0.01), with good awareness associated with reported pain., Conclusion: A significant occurrence of musculoskeletal disorders (MSDs), particularly in the neck, low back, and shoulders. The association was observed with education and ergonomic awareness, age and years of experience with practice and MSD and awareness., Competing Interests: Declaration of competing interest The author declares that they have no Conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Influenza A virus (IAV) infection while primarily affecting the lungs, is often associated with cardiovascular complications. However, the mechanisms underlying this association are not fully understood. Here, we investigated the potential role of FBXL19, a member of the Skp1-Cullin-1-F-box family of E3 ubiquitin ligase, in IAV-induced cardiac inflammation. We demonstrated that FBXL19 overexpression in endothelial cells (ECs) reduced viral titers and IAV matrix protein 1 (M1) levels while increasing antiviral gene expression, including interferon (IFN)-α, -β, and -γ and RANTES (regulated on activation normal T cell expressed and secreted) in the cardiac tissue of IAV-infected mice. Moreover, EC-specific overexpression of FBXL19 attenuated the IAV infection-reduced interferon regulatory factor 3 (IRF3) level without altering its mRNA level and suppressed cardiac inflammation. Furthermore, IAV infection triggered cellular senescence programs in the heart as indicated by the upregulation of p16 and p21 mRNA levels and the downregulation of lamin-B1 levels, which were partially reversed by FBXL19 overexpression in ECs. Our findings indicate that EC-specific overexpression of FBXL19 protects against IAV-induced cardiac damage by enhancing interferon-mediated antiviral signaling, reducing cardiac inflammation, and suppressing cellular senescence programs. NEW & NOTEWORTHY Our study reveals a novel facet of IAV infection, demonstrating that it can trigger cellular senescence within the heart. Intriguingly, upregulation of endothelial FBXL19 promotes host innate immunity, reduces cardiac senescence, and diminishes inflammation. These findings highlight the therapeutic potential of targeting FBXL19 to mitigate IAV-induced cardiovascular complications.

Management of cancer is challenging due to non-targeting and high side effect issues. Drug repurposing is an innovative method for employing medications for other disease therapy in addition to their original use. Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor, is a lipid-lowering drug that is being studied for the treatment of cancer in various in vitro and in vivo models. Nanotechnology offers a potential platform for incorporation of drugs with enhanced pharmaceutical (solubility, release characteristics, stability, etc.) and biological characteristics (targeting, pharmacokinetic, pharmacodynamic). Utilizing a variety of resources such as Scopus, Springer, Web of Science, Elsevier, Bentham Science, Taylor & Francis, and PubMed, a thorough literature search was carried out by looking through electronic records published between 2003 and 2024. The keywords used were simvastatin, drug repurposing, anti-cancer simvastatin, pharmaceutical properties of simvastatin, simvastatin nanoformulations, simvastatin patents, clinical trials, etc. Numerous articles were looked for, filtered, checked out, and incorporated. Pure simvastatin has been researched as a repurposed medication for the treatment of cancer in several in vitro and in vivo models, such as carcinoma of the lung, colon, liver, prostate, breast, and skin. Simvastatin also incorporated into different nanocarriers (nanosuspensions, microparticles/nanoparticles, liposomes, and nanostructured lipid carriers) and showed improvement in solubility, bioavailability, drug loading, release kinetics, and targeting. Clinical trial and patent reports suggest potential of simvastatin in cancer therapy. The preclinical studies of pure simvastatin in in vitro and in vivo models showed the potential for its ability to inhibit cancer cell growth and further incorporation into nanoformulations strengthened its preclinical and pharmaceutical characteristics., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Phytochemicals, plant-derived compounds, are the major components of traditional medicinal plants. Some phytochemicals have restricted applications, due to low bioavailability and less efficacy. However, their medicinal properties can be enhanced by converting them into value-added products for different bioactivities like anti-oxidant, neuroprotective, anti-obesity, anti-neuroinflammatory, anti-microbial, anti-cancer and anti-inflammatory. Microbial transformation is one such process that is generally more specific and makes it possible to modify a compound without making any unwanted alterations in the molecule. This has led to the efficient production of value-added products with important pharmacological properties and the discovery of new active compounds. The present review assimilates the existing knowledge of the microbial transformation of some phytochemicals like eugenol, curcumin, ursolic acid, cinnamaldehyde, piperine, β-carotene, β-sitosterol, and quercetin to value-added products for their application in food, fragrances, and pharmaceutical industries., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: The genetic underpinning of neurodevelopmental disorders (NDDs) in diverse ethnic populations, especially those with high rates of consanguinity, remains largely unexplored. Here, we aim to elucidate genomic insight from 576 well-phenotyped and highly consanguineous (16%) NDD cohort., Methods: We used chromosomal microarray (CMA; N:247), exome sequencing (ES; N:127), combined CMA and ES (N:202), and long-read genome sequencing to identify genetic etiology. Deep clinical multivariate data were coupled with genomic variants for stratification analysis., Results: Genetic diagnosis rates were 17% with CMA, 29.92% with ES, and 37.13% with combined CMA and ES. Notably, children of consanguineous parents showed a significantly higher diagnostic yield (P < .01) compared to those from nonconsanguineous parents. Among the ES-identified pathogenic variants, 36.19% (38/105) were novel, implicating 35 unique genes. Long-read sequencing of seizure participants unresolved by combined test identified expanded FMR1 trinucleotide repeats. Additionally, we identified 2 recurrent X-linked variants in the G6PD in 3.65% (12/329) of NDD participants. These variants were absent in large-population control cohorts and cohort comprising neurodevelopmental and neuropsychiatric populations of European descendants, indicating a possible associated risk factor potentially resulting from ancient genetic drift., Conclusion: This study unveils unique clinical and genomic insights from a consanguinity rich Bangladeshi NDD cohort, highlighting a strong association of G6PD with NDD in this population., Competing Interests: Conflict of Interest Corresponding author, Mohammed Uddin owns share of GenomeArc. All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Geraniol is an important component in essential oils of aromatic plants such as lemongrass, rosa grass, and many others. It can be converted to different high-value products by using microbes/enzymes. The present study aims at the isolation and screening of microbes showing efficient production of geranic acid (a high-value product) from geraniol (a low-value monoterpene). Mucor irregularis IIIMF4011, isolated from the soil sample of Cymbopogon citratus (Lemongrass), showed biotransformation of geraniol to geranic acid. After optimization of reaction parameters, 97-100% conversion of geraniol to geranic acid was obtained after 72 h of incubation at 28 °C. Furthermore, the biotransformation reaction was also carried out in a 3 L fermentor (working volume 1.5 L), and 98.89% conversion was observed. Therefore, an efficient process of geranic acid production using M. irregularis IIIMF4011 was developed., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Lung microvascular endothelial cell (EC) dysfunction is the pathological hallmark of acute respiratory distress syndrome. Heat shock protein 90 (HSP90) is a key regulator in control of endothelial barrier disruption and inflammation. Our recent study has demonstrated that ubiquitin-specific peptidase 40 (USP40) preserves endothelial integrity by targeting HSP90β for its deubiquitination and inactivation. Indole-3-acetic acid (IAA), a plant hormone of the auxin class, can also be catabolized from dietary tryptophan by the intestinal microbiota. Accumulating evidence suggests that IAA reduces oxidative stress and inflammation and promotes intestinal barrier function. However, little is known about the role of IAA in endothelial cells and acute lung injury. In this study, we investigated the role of IAA in lung endothelial cell function in the context of acute lung injury. IAA exhibited EC barrier protection against LPS-induced reduction in transendothelial electrical resistance and inflammatory responses. The underlying mechanism of IAA on EC protective effects was investigated by examining the influence of IAA on degrees of HSP90 ubiquitination and USP40 activity. We identified that IAA, acting as a potential activator of USP40, reduces HSP90 ubiquitination, thereby protecting against LPS-induced inflammation in human lung microvascular endothelial cells as well as alleviating experimental lung injury. Furthermore, the EC protective effects of IAA against LPS-induced EC dysfunction and lung injury were abolished in USP40-deficient human lung microvascular endothelial cell and lungs of USP40 EC-specific knockout (USP40 cdh5-ECKO ) mice. Taken together, this study reveals that IAA protects against LPS-induced EC dysfunction and lung injury through the activation of USP40.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Burnout, characterized by emotional exhaustion (EX), depersonalization (DP), and a reduced sense of personal efficacy (PF) among medical and nursing students can lead to suicidal ideation, lack of empathy, and dropouts. Previous studies have used over-simplified definitions of burnout that fail to capture its complexity. We describe the prevalence of burnout profiles and its risk factors among medical and nursing students., Methods: A cross sectional study was conducted at a tertiary care University Hospital in Pakistan. The Maslach Burnout Inventory (MBI) survey was disseminated via SurveyMonkey over a period of 4 months (November 2019 to February 2020) to 482 Medical and 441 nursing students. The MBI tool measures the dimensions of EX, DP, and PF to describe seven burnout profiles. Multivariable regression was used to identify predictors of burnout., Results: The response rate was 92% in nursing and 87.3% in medical students. The prevalence of burnout in medical and nursing students was 16.9% and 6.7% respectively (p<0.001), with 55.7% (n = 427) suffering from at least one burnout profile. Only 32.5% (n = 250) students felt engaged, (42.3% medical, 22.7% nursing students, p<0.001). The most common profile was ineffective (32.5%, n = 250), characterized by a reduced sense of personal efficacy (35.6% medical, 29.4% nursing students; p = 0.065). Medical students were at higher risk of burnout compared to nursing students (OR = 2.49 [1.42, 4.38]; p<0.001) with highest risk observed in year 4 (OR = 2.47 [1.02, 5.99]; p = 0.046). Other risk factors for burnout included occasional drug use (OR = 1.83 [1.21, 8.49]; p = 0.017) and living in a hostel (OR = 1.64 [1.01,2.67]; p = 0.233)., Conclusion and Relevance: Two-thirds of our participants experienced at least one dimension of burnout with the highest prevalence of a reduced sense of PF. Drivers of burnout unique to a lower-middle-income country need to be understood for effective interventions. Faculty training on principles of student evaluation and feedback may be beneficial., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mufarrih et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fourteen Speech and Language Therapists/Pathologists (SLT/Ps) from 13 countries across 5 continents made up the International Confederation of Cleft Lip and Palate and Related Craniofacial Anomalies (ICCPCA) CLEFT 2022 Speech Taskforce. Following a group consensus activity led by an external facilitator using Lightning Design Thinking principles, "task-shifting" was identified as the topic for this Taskforce. Absence and scarcity of SLT/Ps in many parts of the world have led to non-SLT/Ps delivering speech and language therapy services to individuals with cleft lip +/- palate. This narrative is the first known attempt to develop a framework, describing the different types of providers and their scope of practice., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Mitochondrial dysfunction plays a pivotal role in the development of age-related diseases, particularly neurodegenerative disorders. The etiology of mitochondrial dysfunction involves a multitude of factors that remain elusive. This review centers on elucidating the role(s) of excitotoxicity, oxytosis/ferroptosis and neurodegeneration within the context of mitochondrial bioenergetics, biogenesis, mitophagy and oxidative stress and explores their intricate interplay in the pathogenesis of neurodegenerative diseases. The effective coordination of mitochondrial turnover processes, notably mitophagy and biogenesis, is assumed to be critically important for cellular resilience and longevity. However, the age-associated decrease in mitophagy impedes the elimination of dysfunctional mitochondria, consequently impairing mitochondrial biogenesis. This deleterious cascade results in the accumulation of damaged mitochondria and deterioration of cellular functions. Both excitotoxicity and oxytosis/ferroptosis have been demonstrated to contribute significantly to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS). Excitotoxicity, characterized by excessive glutamate signaling, initiates a cascade of events involving calcium dysregulation, energy depletion, and oxidative stress and is intricately linked to mitochondrial dysfunction. Furthermore, emerging concepts surrounding oxytosis/ferroptosis underscore the importance of iron-dependent lipid peroxidation and mitochondrial engagement in the pathogenesis of neurodegeneration. This review not only discusses the individual contributions of excitotoxicity and ferroptosis but also emphasizes their convergence with mitochondrial dysfunction, a key driver of neurodegenerative diseases. Understanding the intricate crosstalk between excitotoxicity, oxytosis/ferroptosis, and mitochondrial dysfunction holds potential to pave the way for mitochondrion-targeted therapeutic strategies. Such strategies, with a focus on bioenergetics, biogenesis, mitophagy, and oxidative stress, emerge as promising avenues for therapeutic intervention.

A pre-post-training workshop was conducted among 22 postgraduate trainees of the Psychiatry and Emergency Department of a public sector hospital in Karachi. The workshop aimed to build the capacity of postgraduate trainees in trauma management by providing training on screening, clinical interviewing skills, and Psychological first aid to those exposed to domestic violence (DV). The effectiveness of each training module was evaluated by conducting a brief assessment before and after each module and scores were compared using the Wilcoxon signed-rank test. The post-test showed significant improvement in participants' knowledge on screening of domestic violence and trauma symptoms (p = 0.026) and psychological first aid (p <0.001). Postgraduate training programmes need to integrate trauma screening and management education, to prepare healthcare professionals to deal with sensitive clinical presentations at their work settings. Key Words: Postgraduate trainees, Trauma, Domestic violence, Medical education, Workshop.

Background: Insomnia is a prevalent and distressing sleep disorder. Multicomponent cognitive-behavioural therapy is the recommended first-line treatment, but access remains extremely limited, particularly in primary care where insomnia is managed. One principal component of cognitive-behavioural therapy is a behavioural treatment called sleep restriction therapy, which could potentially be delivered as a brief single-component intervention by generalists in primary care., Objectives: The primary objective of the Health-professional Administered Brief Insomnia Therapy trial was to establish whether nurse-delivered sleep restriction therapy in primary care improves insomnia relative to sleep hygiene. Secondary objectives were to establish whether nurse-delivered sleep restriction therapy was cost-effective, and to undertake a process evaluation to understand intervention delivery, fidelity and acceptability., Design: Pragmatic, multicentre, individually randomised, parallel-group, superiority trial with embedded process evaluation., Setting: National Health Service general practice in three regions of England., Participants: Adults aged ≥ 18 years with insomnia disorder were randomised using a validated web-based randomisation programme., Interventions: Participants in the intervention group were offered a brief four-session nurse-delivered behavioural treatment involving two in-person sessions and two by phone. Participants were supported to follow a prescribed sleep schedule with the aim of restricting and standardising time in bed. Participants were also provided with a sleep hygiene leaflet. The control group received the same sleep hygiene leaflet by e-mail or post. There was no restriction on usual care., Main Outcome Measures: Outcomes were assessed at 3, 6 and 12 months. Participants were included in the primary analysis if they contributed at least one post-randomisation outcome. The primary end point was self-reported insomnia severity with the Insomnia Severity Index at 6 months. Secondary outcomes were health-related and sleep-related quality of life, depressive symptoms, work productivity and activity impairment, self-reported and actigraphy-defined sleep, and hypnotic medication use. Cost-effectiveness was evaluated using the incremental cost per quality-adjusted life-year. For the process evaluation, semistructured interviews were carried out with participants, nurses and practice managers or general practitioners. Due to the nature of the intervention, both participants and nurses were aware of group allocation., Results: We recruited 642 participants ( n  = 321 for sleep restriction therapy; n  = 321 for sleep hygiene) between 29 August 2018 and 23 March 2020. Five hundred and eighty participants (90.3%) provided data at a minimum of one follow-up time point; 257 (80.1%) participants in the sleep restriction therapy arm and 291 (90.7%) participants in the sleep hygiene arm provided primary outcome data at 6 months. The estimated adjusted mean difference on the Insomnia Severity Index was -3.05 (95% confidence interval -3.83 to -2.28; p  < 0.001, Cohen's d  = -0.74), indicating that participants in the sleep restriction therapy arm [mean (standard deviation) Insomnia Severity Index = 10.9 (5.5)] reported lower insomnia severity compared to sleep hygiene [mean (standard deviation) Insomnia Severity Index = 13.9 (5.2)]. Large treatment effects were also found at 3 ( d  = -0.95) and 12 months ( d  = -0.72). Superiority of sleep restriction therapy over sleep hygiene was evident at 3, 6 and 12 months for self-reported sleep, mental health-related quality of life, depressive symptoms, work productivity impairment and sleep-related quality of life. Eight participants in each group experienced serious adverse events but none were judged to be related to the intervention. The incremental cost per quality-adjusted life-year gained was £2075.71, giving a 95.3% probability that the intervention is cost-effective at a cost-effectiveness threshold of £20,000. The process evaluation found that sleep restriction therapy was acceptable to both nurses and patients, and delivered with high fidelity., Limitations: While we recruited a clinical sample, 97% were of white ethnic background and 50% had a university degree, which may limit generalisability to the insomnia population in England., Conclusions: Brief nurse-delivered sleep restriction therapy in primary care is clinically effective for insomnia disorder, safe, and likely to be cost-effective., Future Work: Future work should examine the place of sleep restriction therapy in the insomnia treatment pathway, assess generalisability across diverse primary care patients with insomnia, and consider additional methods to enhance patient engagement with treatment., Trial Registration: This trial is registered as ISRCTN42499563., Funding: The award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/84/01) and is published in full in Health Technology Assessment ; Vol. 28, No. 36. See the NIHR Funding and Awards website for further award information.

Background: Previous studies present mixed evidence on the relationship between psychiatric comorbidities and genital gender-affirming surgery (GGAS) in individuals with gender incongruence (GI)., Aim: This research aims to investigate the psychiatric comorbidity rates post-GGAS in the GI population-namely, depressive disorders, anxiety disorders, posttraumatic stress disorders, substance abuse disorder, and suicidality., Methods: Based on the TriNetX health care database, an international database with >250 million patients, a cross-sectional study was executed comparing psychiatric comorbidity rates among cases of GI with and without GGAS. Individuals were matched for demographic and health-related variables, which included history of cardiovascular disease, diabetes, and obesity., Outcomes: The main focus was to establish the rates and changes in psychiatric comorbidities following GGAS., Results: Among individuals with GI, the study identified 4061 with GGAS and 100 097 without. At 1 year post-GGAS, there was a significant decrease in depression (odds ratio [OR], 0.748; 95% CI, 0.672-0.833; P < .0001), anxiety (OR, 0.730; 95% CI, 0.658-0.810; P < .0001), substance use disorder (OR, 0.730; 95% CI, 0.658-0.810; P < .0001), and suicidality (OR, 0.530; 95% CI, 0.425-0.661; P < .0001), and these reductions were maintained or improved on at 5 years, including posttraumatic stress disorder (OR, 0.831; 95% CI, 0.704-0.981; P = .028)., Clinical Implications: The findings indicate that GGAS may play a crucial role in diminishing psychiatric comorbidities among individuals with GI., Strengths and Limitations: This is the largest known study to evaluate the effect of GGAS on psychiatric comorbidities in the GI population, offering robust evidence. The reliance on the precision of CPT and ICD-10 codes for data extraction poses a limitation due to potential coding inaccuracies., Conclusion: The evidence suggests a significant association between GGAS and reduced psychiatric comorbidities in individuals with GI., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study explores copyrolysis of soybean straw (SS) with hydrogen-rich tire waste (TW) to enhance pyrolytic product quality and reduce pollutant emissions. Addition of TW increased SS biomass conversion from 67.19 to 72.46% and decreased coke/residue formation from 32.81 to 27.54%. The activation energy dropped to 121.84 kJ/mol from 160.73 kJ/mol (as calculated by the Kissinger-Akahira-Sunose method) and 122.78 kJ/mol from 159.76 kJ/mol (as calculated by the Ozawa-Flynn-Wall method). Thermogravimetric analysis coupled with Fourier-transform infrared spectroscopy (TG-FTIR) showed lowered CO 2 , NO 2 , and SO 2 emissions (5.58, 5.72, 3.38) compared to conventional SS pyrolysis (18.38, 11.55, 12.37). Yields of value-added chemicals (phenols, olefins, aromatics) increased (32.38, 22.17, 30.18%) versus conventional SS pyrolysis (23.56, 13.78, 20.36%). Pyrolysis gas chromatography-mass spectrometry (Py/GC-MS) analysis reveals that the addition of TW leads to a decrease in the production of oxygenates and polycyclic aromatic hydrocarbons, reducing their yields to 8.96 and 7.67%, respectively, down from 19.37 and 14.37%. Simultaneously, it enhances the yields of olefins, aromatics, phenols, and aliphatic hydrocarbons to 23.38, 26.78, 26.17, and 25.78%, respectively, compared to 15.37%, 15.29, 18.36, and 17.25%, respectively, in the absence of TW. In summary, copyrolysis of TW with SS improves product quality and reduces pollutant emissions, marking a significant research contribution., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Genome replication is frequently impeded by highly stable DNA secondary structures, including G-quadruplex (G4) DNA, that can hinder the progression of the replication fork. Human WRNIP1 (Werner helicase Interacting Protein 1) associates with various components of the replication machinery and plays a crucial role in genome maintenance processes. However, its detailed function is still not fully understood. Here we show that human WRNIP1 interacts with G4 structures and provide evidence for its contribution to G4 processing. The absence of WRNIP1 results in elevated levels of G4 structures, DNA damage and chromosome aberrations following treatment with PhenDC3, a G4-stabilizing ligand. Additionally, we establish a functional and physical relationship between WRNIP1 and the PIF1 helicase in G4 processing. In summary, our results suggest that WRNIP1 aids genome replication and maintenance by regulating G4 processing and this activity relies on Pif1 DNA helicase., (© 2024. The Author(s).)

Background: The optimal management of breech presentation remains a debate among obstetricians worldwide. The Term Breech Trial (2000) highlighted elective caesarean section as a preferable method over vaginal delivery for breech presentations. This study investigates delivery modes in women who had an elective caesarean section for breech presentation in their first pregnancy. Objective was to evaluate delivery outcomes in the second pregnancy of women who had an elective caesarean section for breech presentation in their first pregnancy., Methods: A cross-sectional study was conducted at Jinnah International Hospital Abbottabad from October 10, 2018, to April 10, 2019. Data was collected from 321 women who had an elective caesarean section for breech presentation during their first pregnancy. The study used per-abdominal examination and obstetrical ultrasound to assess foetal presentation and recorded the mode of delivery in the second pregnancy., Results: Participants' ages ranged from 18 to 49 years, with a mean age of 28.87±4.07 years. The average interval between deliveries was 1.92±0.92 years, labour duration averaged 5.56±2.41 hours, and foetal head engagement averaged 2.92±1.35. Of the participants, 18.7% achieved a vaginal delivery, while 81.3% had a repeat caesarean section. Reasons for repeat caesarean included recurrent breech presentation in 44.9% and foetal distress in 32.4%., Conclusions: Approximately 18.7% of women who had an elective caesarean section for breech presentation in their first pregnancy achieved vaginal delivery in their second pregnancy, whereas the majority underwent another elective caesarean section.

Background: Deep inferior epigastric perforator (DIEP) flap breast reconstruction is among the higher-risk patient groups for venous thromboembolism (VTE) in plastic surgery. Surgeons often opt for a patient-specific approach to postoperative anticoagulation, and the field has yet to come to a consensus on VTE chemoprophylaxis regimens., Methods: A new chemoprophylaxis protocol was introduced starting in March of 2019 that involved 2 weeks of treatment with enoxaparin, regardless of patient risk factors. A retrospective chart review was conducted on all patients who underwent DIEP flap breast reconstruction at the authors' institution between January of 2014 and March of 2020. Patients were grouped based on whether they enrolled in the new VTE protocol in the postoperative period or not. Patient demographics, prophylaxis type, and outcomes data were recorded, retrospectively. The primary outcome measure was postoperative VTE incidence., Results: Risk of VTE was significantly higher in patients discharged without VTE prophylaxis compared with patients discharged with prophylaxis (3.7% versus 0%; P = 0.03). Notably, zero patients in the VTE prophylaxis group developed a deep venous thrombosis or pulmonary embolism. In addition, the risk of a VTE event was 25 times greater in patients with a Caprini score greater than or equal to 6 ( P = 0.0002)., Conclusion: The authors demonstrate the successful implementation of a 2-week VTE chemoprophylaxis protocol in DIEP flap breast reconstruction patients that significantly reduces the rate of VTE while not affecting the rate of hematoma complications., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

STAT1 (Signal Transducer and Activator of Transcription 1), belongs to the STAT protein family, essential for cytokine signaling. It has been reported to have either context dependent oncogenic or tumor suppressor roles in different tumors. Earlier, we demonstrated that Glioblastoma multiforme (GBMs) overexpressing FAT1, an atypical cadherin, had poorer outcomes. Overexpressed FAT1 promotes pro-tumorigenic inflammation, migration/invasion by downregulating tumor suppressor gene, PDCD4. Here, we demonstrate that STAT1 is a novel mediator downstream to FAT1, in downregulating PDCD4 in GBMs. In-silico analysis of GBM databases as well as q-PCR analysis in resected GBM tumors showed positive correlation between STAT1 and FAT1 mRNA levels. Kaplan-Meier analysis showed poorer survival of GBM patients having high FAT1 and STAT1 expression. SiRNA-mediated knockdown of FAT1 decreased STAT1 and increased PDCD4 expression in glioblastoma cells (LN229 and U87MG). Knockdown of STAT1 alone resulted in increased PDCD4 expression. In silico analysis of the PDCD4 promoter revealed four putative STAT1 binding sites (Site1-Site4). ChIP assay confirmed the binding of STAT1 to site1. ChIP-PCR revealed decrease in the binding of STAT1 on the PDCD4 promoter after FAT1 knockdown. Site directed mutagenesis of Site1 resulted in increased PDCD4 luciferase activity, substantiating STAT1 mediated PDCD4 inhibition. EMSA confirmed STAT1 binding to the Site 1 sequence. STAT1 knockdown led to decreased expression of pro-inflammatory cytokines and EMT markers, and reduced migration/invasion of GBM cells. This study therefore identifies STAT1 as a novel downstream mediator of FAT1, promoting pro-tumorigenic activity in GBM, by suppressing PDCD4 expression., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Porous organic frameworks (POFs) represent a significant subclass of nanoporous materials in the field of materials science, offering exceptional characteristics for advanced applications. Covalent organic frameworks (COFs), as a novel and intriguing type of porous material, have garnered considerable attention due to their unique design capabilities, diverse nature, and wide-ranging applications. The unique structural features of COFs, such as high surface area, tuneable pore size, and chemical stability, render them highly attractive for various applications, including targeted and controlled drug release, as well as improving the sensitivity and selectivity of electrochemical biosensors. Therefore, it is crucial to comprehend the methods employed in creating COFs with specific properties that can be effectively utilized in biomedical applications. To address this indispensable fact, this review paper commences with a concise summary of the different methods and classifications utilized in synthesizing COFs. Second, it highlights the recent advancements in COFs for drug delivery, including drug carriers as well as the classification of drug delivery systems and biosensing, encompassing drugs, biomacromolecules, small biomolecules and the detection of biomarkers. While exploring the potential of COFs in the biomedical field, it is important to acknowledge the limitations that researchers may encounter, which could impact the practicality of their applications. Third, this paper concludes with a thought-provoking discussion that thoroughly addresses the challenges and opportunities associated with leveraging COFs for biomedical applications. This review paper aims to contribute to the scientific community's understanding of the immense potential of COFs in improving drug delivery systems and enhancing the performance of biosensors in biomedical applications., (© 2024 Wiley Periodicals LLC.)

The field of nutrigenomics studies the interaction between nutrition and genetics, and how certain dietary patterns can impact gene expression and overall health. The Mediterranean diet (MedDiet), characterized by a high intake of fruits, vegetables, whole grains, and healthy fats, has been linked to better cardiovascular health (CVH) outcomes. This review summarizes the current state of research on the effects of nutrigenomics and MedDiet on cardiovascular health. Results suggest that MedDiet, through its impact on gene expression, can positively influence CVH markers such as blood pressure, lipid profile, and inflammation. However, more research is needed to fully understand the complex interactions between genetics, nutrition, and CVH, and to determine the optimal dietary patterns for individualized care. The aim of this scientific review is to evaluate the current evidence on the effects of nutrigenomics and MedDiet on cardiovascular health. The review summarizes the available studies that have investigated the relationship between nutrition, genetics, and cardiovascular health, and explores the mechanisms by which certain dietary patterns can impact CVH outcomes. The review focuses on the effects of MedDiet, a dietary pattern that is rich in whole foods and healthy fats, and its potential to positively influence CVH through its impact on gene expression. The review highlights the limitations of current research and the need for further studies to fully understand the complex interplay between nutrition, genetics, and cardiovascular health.

Canola, a vital oilseed crop, is grown globally for food and biodiesel. With the enormous demand for growing various crops, the utilization of agriculturally marginal lands is emerging as an attractive alternative, including brackish-saline transitional lands. Salinity is a major abiotic stress limiting growth and productivity of most crops, and causing food insecurity. Salicylic acid (SA), a small-molecule phenolic compound, is an essential plant defense phytohormone that promotes immunity against pathogens. Recently, several studies have reported that SA was able to improve plant resilience to withstand high salinity. For this purpose, a pot experiment was carried out to ameliorate the negative effects of sodium chloride (NaCl) on canola plants through foliar application of SA. Two canola varieties Faisal (V1) and Super (V2) were assessed for their growth performance during exposure to high salinity i.e. 0 mM NaCl (control) and 200 mM NaCl. Three levels of SA (0, 10, and 20 mM) were applied through foliar spray. The experimental design used for this study was completely randomized design (CRD) with three replicates. The salt stress reduced the shoot and root fresh weights up to 50.3% and 47% respectively. In addition, foliar chlorophyll a and b contents decreased up to 61-65%. Meanwhile, SA treatment diminished the negative effects of salinity and enhanced the shoot fresh weight (49.5%), root dry weight (70%), chl. a (36%) and chl. b (67%). Plants treated with SA showed an increased levels of both enzymatic i.e. (superoxide dismutase (27%), peroxidase (16%) and catalase (34%)) and non-enzymatic antioxidants i.e. total soluble protein (20%), total soluble sugar (17%), total phenolic (22%) flavonoids (19%), anthocyanin (23%), and endogenous ascorbic acid (23%). Application of SA also increased the levels of osmolytes i.e. glycine betaine (31%) and total free proline (24%). Salinity increased the concentration of Na + ions and concomitantly decreased the K + and Ca 2+ absorption in canola plants. Overall, the foliar treatments of SA were quite effective in reducing the negative effects of salinity. By comparing both varieties of canola, it was observed that variety V2 (Super) grew better than variety V1 (Faisal). Interestingly, 20 mM foliar application of SA proved to be effective in ameliorating the negative effects of high salinity in canola plants., (© 2024. The Author(s).)

Aims: To describe the ultrasound diagnostic features and surgical management procedures for patients with an interstitial ectopic pregnancy in our tertiary institution and associated peripheral hospital over a ten-year period., Methods: A retrospective audit of all surgically managed cases of interstitial pregnancies over a ten-year period at a tertiary hospital and one associated peripheral hospital in New South Wales., Results: Sixteen cases of surgically managed interstitial pregnancy were identified. In 43.8% of these cases, patients had previously undergone an ipsilateral salpingectomy. No cases required hysterectomy, post-operative methotrexate or return to theatre. Ten patients underwent diagnostic ultrasound prior to operative management, seven of which were correctly identified to be an interstitial ectopic pregnancy at the time. The proportion of cornuostomies being performed for interstitial pregnancy compared to wedge resection has increased over the period of this review from 33 to 60% between the two five-year periods., Conclusion: The combination of expert ultrasound and sophisticated laparoscopic techniques at our institution has facilitated earlier diagnosis and greater use of minimally invasive management of interstitial pregnancy., (© 2024 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Pain is a multifaceted, multisystem disorder that adversely affects neuro-psychological processes. This study compares the effectiveness of central stimulation (transcranial direct current stimulation-tDCS over F3/F4) and peripheral stimulation (transcutaneous electrical nerve stimulation-TENS over the median nerve) in pain inhibition during a cognitive task in healthy volunteers and to observe potential neuro-cognitive improvements. Eighty healthy participants underwent a comprehensive experimental protocol, including cognitive assessments, the Cold Pressor Test (CPT) for pain induction, and tDCS/TENS administration. EEG recordings were conducted pre- and post-intervention across all conditions. The protocol for this study was categorized into four groups: G1 (control), G2 (TENS), G3 (anodal-tDCS), and G4 (cathodal-tDCS). Paired t -tests ( p < 0.05) were conducted to compare Pre-Stage, Post-Stage, and neuromodulation conditions, with t-values providing insights into effect magnitudes. The result showed a reduction in pain intensity with TENS ( p = 0.002, t-value = -5.34) and cathodal-tDCS ( p = 0.023, t-value = -5.08) and increased pain tolerance with TENS ( p = 0.009, t-value = 4.98) and cathodal-tDCS ( p = 0.001, t-value = 5.78). Anodal-tDCS ( p = 0.041, t-value = 4.86) improved cognitive performance. The EEG analysis revealed distinct neural oscillatory patterns across the groups. Specifically, G2 and G4 showed delta-power reductions, while G3 observed an increase. Moreover, G2 exhibited increased theta-power in the occipital region during CPT and Post-Stages. In the alpha-band, G2, G3, and G4 had reductions Post-Stage, while G1 and G3 increased. Additionally, beta-power increased in the frontal region for G2 and G3, contrasting with a reduction in G4. Furthermore, gamma-power globally increased during CPT1, with G1, G2, and G3 showing reductions Post-Stage, while G4 displayed a global decrease. The findings confirm the efficacy of TENS and tDCS as possible non-drug therapeutic alternatives for cognition with alleviation from pain.

Introduction: The overall prevalence of cigarette smoking has not changed significantly for over a decade in Bangladesh. Raising the price of cigarettes through taxation is an important policy instrument for reducing consumption and achieving public health goals. The price elasticity of cigarette demand is an important parameter for evaluating the effectiveness of raising prices through tax increases in reducing cigarette consumption. The objective of the study was to estimate the price elasticity of cigarette demand in Bangladesh using Global Adult Tobacco Survey 2009 and 2017 data., Methods: Smoking prevalence and smoking intensity were estimated using a two-part model. Endogeneity of prices was minimised using the average consumption-weighted cigarette price in a cluster, for both smokers and non-smokers residing in a specific cluster., Results: Cigarette demand was found to be price inelastic and ranged between -0.51 and -0.73. It is also price inelastic across wealth groups and areas of residence in Bangladesh. Although the total price elasticity did not differ considerably between rural and urban locations, it is evident that individuals in the lower-wealth group are more than twice as responsive to price increases as their high-wealth counterparts., Conclusion: A significant increase in cigarette prices through a tax increase would decrease smoking prevalence and increase tax revenue in Bangladesh. The greater price sensitivity among smokers in lower-wealth groups indicates that a tax-induced cigarette price increase would provide more health benefits to them, thereby contributing to improved health equity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: The overall price elasticity of cigarette consumption in Bangladesh has been studied extensively. The estimates of price elasticity by price tiers are not available in the existing literature., Methods: Using cohort data of nearly 6000 individuals from the International Tobacco Control Bangladesh survey, this study estimated the own-price and cross-price elasticity and income elasticity of cigarette demand by price tiers in Bangladesh. The elasticity was estimated in three stages of consumer decisions: whether to smoke, which brand to smoke and finally, how many cigarettes to smoke per day. The decision to smoke cigarettes and the choice of cigarette brands were modelled using instrumental variable probability regression. The cigarette consumption per day was modelled using seemingly unrelated regression., Results: The price elasticity of cigarette smoking prevalence with respect to the price of low-price cigarettes is -0.0487. The total elasticity for low-price cigarette consumption with respect to its own price is -0.1678. The own-price elasticity of smoking intensity of high-priced brands is -0.2512. The cross-price elasticity of low-price cigarette consumption with respect to high-price brand prices is 0.2643. The income elasticity of smoking prevalence overall is 0.0564. The income elasticity of daily consumption of low-price cigarettes is -0.1934 and for high-price cigarettes, it is 1.4044. The total income elasticity is 1.4608 for high-price cigarettes., Conclusion: A cigarette tax policy that raises the prices of both low-price and high-price brands-but increases prices in the low-price tier at a faster rate than in the high-price tier and increases prices of all brands at a pace faster than income growth-can effectively reduce cigarette consumption in Bangladesh., Jel Codes: H29, L66, I18., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The Dental Practicality Index (DPI) has been designed to describe, on a clinical level, the 'practicality' of restoring a tooth versus referring to secondary care or extraction.The systematic approach of DPI has been shown to improve decision-making and confidence in treatment planning when used by young dentists. In addition, there is good evidence demonstrating that it provides an accurate estimation of the outcome of treatment. The DPI enhances clinician-patient communication and ultimately the consent process., (© 2024. The Author(s), under exclusive licence to the British Dental Association.)