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Olfactory perception is an important physiological function for human well-being and health. Loss of olfaction, or anosmia, caused by viral infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has received considerable attention, especially in persistent cases that take a long time to recover. This review discusses the integration of different components of the olfactory epithelium to serve as a structural and functional unit and explores how they are affected during viral infections, leading to the development of olfactory dysfunction. The review mainly focused on the role of receptors mediating the disruption of olfactory signal transduction pathways such as angiotensin converting enzyme 2 (ACE2), transmembrane protease serine type 2 (TMPRSS2), neuropilin 1 (NRP1), basigin (CD147), olfactory, transient receptor potential vanilloid 1 (TRPV1), purinergic, and interferon gamma receptors. Furthermore, the compromised function of the epithelial sodium channel (ENaC) induced by SARS-CoV-2 infection and its contribution to olfactory dysfunction are also discussed. Collectively, this review provides fundamental information about the many types of receptors that may modulate olfaction and participate in olfactory dysfunction. It will help to understand the underlying pathophysiology of virus-induced anosmia, which may help in finding and designing effective therapies targeting molecules involved in viral invasion and olfaction. To the best of our knowledge, this is the only review that covered all the receptors potentially involved in, or mediating, the disruption of olfactory signal transduction pathways during COVID-19 infection. This wide and complex spectrum of receptors that mediates the pathophysiology of olfactory dysfunction reflects the many ways in which anosmia can be therapeutically managed.

Lipid-bilayer-based liposomes are gaining attention in scientific research for their versatile role in drug delivery. With their amphiphilic design, liposomes efficiently encapsulate and deliver drugs to targeted sites, offering controlled release. These artificial structures hold great promise in advancing cancer therapy methodologies. Bibliometric research analyzes systematic literary data statistically. This study used bibliometric indicators to examine, map, and evaluate the applications of liposomes in cancer therapy. A Scopus search was conducted to identify all English-language peer-reviewed scientific publications on the applications of liposomes in cancer therapy within the past twenty years. Bibliometric indicators were calculated using VOSviewer and Biblioshiny. We produced thematic, conceptual, and visualization charts. A total of 14,873 published documents were obtained. The procedure of keyword mapping has effectively identified the main areas of research concentration and prevailing trends within this specific field of study. The significant clusters discovered through theme and hotspot analyses encompassed many topics such as the use of multiple strategies in chemotherapy and different forms of cancer, the study of pharmacokinetics and nanomedicine, as well as the investigation of targeted drug delivery, cytotoxicity, and gene delivery. Liposomes were employed as drug delivery systems so as to selectively target cancer cells and improve the bioavailability of anticancer drugs. The work showcased the capacity to tailor these liposomes for accurate drug delivery by including potent anticancer medications. Our findings not only bring attention to the latest progress in utilizing liposomes for cancer treatment but also underscore the vital need for ongoing research, collaborative efforts, and the effective translation of these breakthroughs into tangible clinical applications, emphasizing the dynamic and evolving nature of cancer therapeutics.

Hypoxia-inducible factor-1 (HIF-1) is a key regulator for balancing oxygen in the cells. It is a transcription factor that regulates the expression of target genes involved in oxygen homeostasis in response to hypoxia. Recently, research has demonstrated the multiple roles of HIF-1 in the pathophysiology of various diseases, including cancer. It is a crucial mediator of the hypoxic response and regulator of oxygen metabolism, thus contributing to tumor development and progression. Studies showed that the expression of the HIF-1α subunit is significantly upregulated in cancer cells and promotes tumor survival by multiple mechanisms. In addition, HIF-1 has potential contributing roles in cancer progression, including cell division, survival, proliferation, angiogenesis, and metastasis. Moreover, HIF-1 has a role in regulating cellular metabolic pathways, particularly the anaerobic metabolism of glucose. Given its significant and potential roles in cancer development and progression, it has been an intriguing therapeutic target for cancer research. Several compounds targeting HIF-1-associated processes are now being used to treat different types of cancer. This review outlines emerging therapeutic strategies that target HIF-1 as well as the relevance and regulation of the HIF-1 pathways in cancer. Moreover, it addresses the employment of nanotechnology in developing these promising strategies.

Ultra-processed foods (UPF) are ubiquitous in the modern-day food supply and widely consumed. High consumption of these foods has been suggested to contribute to the development of obesity in adults. The purpose of this review is to present and evaluate current literature on the relationship between UPF consumption and adult obesity. Cross-sectional studies (n = 9) among different populations worldwide show a positive association between UPF consumption and obesity. Longitudinal studies (n = 7) further demonstrate a positive association between UPF consumption and development of obesity, suggesting a potential causal influence of UPF consumption on obesity risk. However, only one randomized controlled trial has tested the causality of this association. The study included in this review found greater energy intake and weight gain with consumption of a high UPF diet compared to a high unprocessed food diet. The potential mechanisms by which UPF increase the risk of obesity include increased energy intake due to increased sugar consumption, decreased fiber consumption, and decreased protein density; however, more research is needed. Overall, the evidence identified in the current review consistently support a positive relation between high UPF consumption and obesity. While there is a need for more experimental research to establish causality and elucidate the mechanisms, the sum of the evidence supports a need for research on treatment modalities that include reductions in UPF consumption for the management of adult obesity., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Urinary stone disease is common and affects approximately 10% of the American adults. The role of diet in stone formation is well-recognized; however, the literature focus has been on dietary excess rather than micronutrient inadequacy. As patients with stones may be at risk for nutrient inadequacies, we investigated the role of micronutrient inadequacy in stone formation by performing a cross-sectional analysis of the National Health and Nutrition Examination Survey on adults who were not taking dietary supplements. Micronutrient intake was obtained from 24-h dietary recalls, and usual intake was calculated. Survey-weighted, adjusted logistic regression was used for an incident analysis on having any history of stones. An additional analysis on recurrent stone-formers was performed with the outcome being 2 or more stones passed. Finally, a sensitivity analysis using quasi-Poisson regression was performed with the outcome being number of stones passed. There were 9777 respondents representing 81,087,345 adults, of which 9.36% had a stone history. Our incident analysis revealed inadequate vitamin A intake to be associated with stone formation (OR 1.33, 95% CI: 1.03-1.71). Recurrent analysis did not find any significant associations, while our sensitivity analysis revealed inadequate vitamin A (IRR 1.96, 95% CI: 1.28-3.00) and pyridoxine (IRR 1.99, 95% CI: 1.11-3.55) to be associated with a higher number of recurrent stones. Hence, inadequate dietary intake of vitamin A and pyridoxine was associated with nephrolithiasis. Further research is needed to identify the roles of these micronutrients in stone-formers and the potential for evaluation and treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Various federal policies have weakened school meal nutrition standards in the United States since the passage of the Healthy, Hunger-Free Kids Act in 2010, including temporary school meal nutrition waivers to promote post-COVID-19 pandemic recovery. This study used school menu and nutrient data from a nationally representative sample of 128 elementary school districts to examine differences in nutrients (average calories, total fat, saturated fat, sodium, total sugar, and fiber) and alignment with United States Department of Agriculture (USDA) sodium targets in 2019 (pre-pandemic) and in 2022 (post-pandemic). Data were analyzed using analysis of variance accounting for repeated measures within school districts, adjusting for geographic region and urbanicity. Small differences in the nutrient content for both breakfast and lunch were observed between 2019 and 2022. Most weeks met USDA sodium Target 1 for breakfast (≥95% of weeks) and Target 1 (≥96% of weeks) and Target 1A for lunch (≥92% of weeks) in both 2019 and 2022, although compliance decreased slightly when condiments were included. Additionally, meals provided on average 57 g of total sugar. Overall, many meals are already in alignment with lower sodium targets. Simple strategies, such as offering lower sodium condiments, can further reduce sodium in school meals. The total sugar levels observed highlight that the USDA should consider limits on added sugars in school meals.

Transient receptor potential vanilloid 1 (TRPV1), a non-selective ligand-gated cation channel with high permeability for Ca 2+ , has received considerable attention as potential therapeutic target for the treatment of several disorders including pain, inflammation, and hyperlipidemia. In particular, TRPV1 regulates lipid metabolism by mechanisms that are not completely understood. Interestingly, TRPV1 and lipids regulate each other in a reciprocal and complex manner. This review surveyed the recent literature dealing with the role of TRPV1 in the hyperlipidemia-associated metabolic syndrome. Besides TRPV1 structure, molecular mechanisms underlying the regulatory effect of TRPV1 on lipid metabolism such as the involvement of uncoupling proteins (UCPs), ATP-binding cassette (ABC) transporters, peroxisome proliferation-activated receptors (PPAR), sterol responsive element binding protein (SREBP), and hypoxia have been discussed. Additionally, this review extends our understanding of the lipid-dependent modulation of TRPV1 activity through affecting both the gating and the expression of TRPV1. The regulatory role of different classes of lipids such as phosphatidylinositol (PI), cholesterol, estrogen, and oleoylethanolamide (OEA), on TRPV1 has also been addressed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abdalla, Harb, Almasri and Bustanji.)

Background: The COVID-19 pandemic created barriers to participation in school meals. As a result, many students may have missed out on school meals. The objectives of this study are (1) to compare the number of school meals served by New York State public schools during the first spring and summer of the COVID-19 pandemic to the number served before the COVID-19 pandemic, and (2) to determine relationships between the number of meals served and the levels of school district need and urbanicity., Methods: This study is a secondary analysis of administrative data. The percentage change in the number of school breakfasts and lunches served was calculated for each month and by school district need level and urbanicity level., Results: The number of school meals served decreased during the first spring of the pandemic compared to the spring of the previous school year (-43% in April, -51% in May), while the number of school meals served increased during the first summer of the pandemic compared to the summer of the previous school year (+92% in July, +288% in August)., Conclusions: Waivers may provide flexibility to increase participation in school meals, especially during the summer.

Objective: To characterise the long-term outcomes of patients with COVID-19 admitted to a large New York City medical centre at 3 and 6 months after hospitalisation and describe their healthcare usage, symptoms, morbidity and mortality., Design: Retrospective cohort through manual chart review of the electronic medical record., Setting: NewYork-Presbyterian/Columbia University Irving Medical Center, a quaternary care academic medical centre in New York City., Participants: The first 1190 consecutive patients with symptoms of COVID-19 who presented to the hospital for care between 1 March and 8 April 2020 and tested positive for SARS-CoV-2 on reverse transcriptase PCR assay., Main Outcome Measures: Type and frequency of follow-up encounters, self-reported symptoms, morbidity and mortality at 3 and 6 months after presentation, respectively; patient disposition information prior to admission, at discharge, and at 3 and 6 months after hospital presentation., Results: Of the 1190 reviewed patients, 929 survived their initial hospitalisation and 261 died. Among survivors, 570 had follow-up encounters (488 at 3 months and 364 at 6 months). An additional 33 patients died in the follow-up period. In the first 3 months after admission, most encounters were telehealth visits (59%). Cardiopulmonary symptoms (35.7% and 28%), especially dyspnoea (22.1% and 15.9%), were the most common reported symptoms at 3-month and 6-month encounters, respectively. Additionally, a large number of patients reported generalised (26.4%) or neuropsychiatric (24.2%) symptoms 6 months after hospitalisation. Patients with severe COVID-19 were more likely to have reduced mobility, reduced independence or a new dialysis requirement in the 6 months after hospitalisation., Conclusions: Patients hospitalised with SARS-CoV-2 infection reported persistent symptoms up to 6 months after diagnosis. These results highlight the long-term morbidity of COVID-19 and its burden on patients and healthcare resources., Competing Interests: Competing interests: GH reports grants from Janssen Research, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with dementia are vulnerable during the coronavirus disease 2019 (COVID-19) pandemic, yet few studies describe their hospital course and outcomes., Objective: To describe and compare the hospital course for COVID-19 patients with dementia to an aging cohort without dementia in a large New York City academic medical center., Methods: This was a single-center retrospective cohort study describing all consecutive patients age 65 or older with confirmed COVID-19 who presented to the emergency department or were hospitalized at New York-Presbyterian/Columbia University Irving Medical Center between March 6 and April 7, 2020., Results: A total of 531 patients were evaluated, including 116 (21.8%) with previously diagnosed dementia, and 415 without dementia. Patients with dementia had higher mortality (50.0%versus 35.4%, p = 0.006); despite similar comorbidities and complications, multivariate analysis indicated the association was dependent on age, sex, comorbidities, and code status. Patients with dementia more often presented with delirium (36.2%versus 11.6%, p < 0.001) but less often presented with multiple other COVID-19 symptoms, and these findings remained after adjusting for age and sex., Conclusion: Hospitalized COVID-19 patients with dementia had higher mortality, but dementia was not an independent risk factor for death. These patients were approximately 3 times more likely to present with delirium but less often manifested or communicated other common COVID-19 symptoms. For this high-risk population in a worsening pandemic, understanding the unique manifestations and course in dementia and aging populations may help guide earlier diagnosis and optimize medical management.

Objective: Achillea fragrantissima L. (Asteraceae) is a traditionally used medicinal herb in the rural communities of Jordan., Methods: The present study evaluated the efficacy of the ethanol extract of this species on angiogenesis in both, ex vivo using a rat aortic ring assay and in vivo using a rat excision wound model., Results: In concentrations of 50 and 100 μg/ml, the ethanol extract showed angiogenic stimulatory effect and significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings. In MCF-7 cells, the ethanol extract of A. fragrantissima stimulated the production of VEGF in a dose-dependent manner. 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment was applied on rat excision wounds for six days and found to be effective in wound healing and maturation of the scar. Both preparations resulted in better wound healing when compared to the untreated control group and vaseline- treated group. This effect was comparable to that induced by MEBO, the positive control., Conclusion: The results indicate that A. fragrantissima has a pro-angiogenic effect, which may act through the VEGF signaling pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background:  End-to-side (ETS) anastomoses are necessary for many procedures in microvascular surgery, such as free flap transfers. In training courses that use the rat model, the arterial end to venous side (AEVS) anastomosis is a common training exercise for ETS anastomoses. Surgeons-in-training often inadvertently twist the artery when completing the AEVS anastomosis; however, in the clinical setting, torsion is a reported risk factor for ETS anastomosis failure. The purpose of this study was to determine if torsion in an AEVS anastomosis would have a negative effect on patency in the rat model, accurately simulating the clinical scenario., Methods:  All AEVS anastomoses were completed in 15 Sprague-Dawley rats divided into three torsion cohorts: 0, 90, and 180 degrees. Torsion was created in the AEVS anastomosis by mismatching the first two sutures placed between the free femoral artery end and the venotomy. Patency was verified at 0, 2, and 4 hours postoperation via the oxygenated-deoxygenated test and transit-time ultrasound blood flow measurements., Results:  All AEVS anastomoses were patent 0, 2, and 4 hours postoperation according to both the oxygenated-deoxygenated test and transit-time ultrasound blood flow measurements. For the average blood flow measurements at 4 hours postoperation, the proximal measurements for 0, 90, and 180 degrees were -34.3, -18.7, and -13.8 mL/min respectively, and the distal measurements were 4.48, 3.46, and 2.90 mL/min, respectively., Conclusion:  Torsion of 180 degrees does not affect early AEVS anastomosis patency in the rat model. This contrasts with the clinical setting, where torsion is reported to cause ETS anastomosis failure. Since AEVS anastomosis torsion is often difficult to appreciate visually, we suggested that microvascular surgery training instructors include a method to both detect and prevent AEVS anastomosis torsion, such as by marking the free femoral artery end with a marking pen or suture before beginning the anastomosis., Competing Interests: M.A.L., A.A.H., C.F.N., J.J.C., A.K., Y.A., R.K.K., and R.J.S. report grants from Orthopedic Scientific Research Foundation, during the conduct of the study., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Lymphedema is a frequent complication after surgical treatments of cancer involving lymph node resection. However, research of lymphedema treatments, such as vascularized lymph node transfer, is limited by the absence of an adequate lymphedema animal model. The purpose of this study was to determine if we could create sustainable lower limb lymphedema in the rat with a combination of inguinal lymphadenectomy, circumferential skin and subcutaneous tissue excision, and radiotherapy., Methods: Inguinal lymphadenectomies were completed in 15 Sprague-Dawley rats. In cohort A, 5 rats received a 0.5- to 1.0-cm wide excision of proximal thigh skin and subcutaneous tissue. This step was omitted for the 10 rats in cohort B. Cohort A then received a single radiation dose of 22.7 Gy, whereas cohort B received a cumulative dose of 40.5 Gy. Bioimpedance measurements were obtained monthly to assess lymphedema progression, and lymphatic drainage at 6 months postradiation was visualized via indocyanine green (ICG) lymphangiography., Results: Two rats in cohort A developed visually appreciable lymphedema in the lower limb, with bioimpedance ratios of 0.684 and 0.542 and ankle circumference ratios of 1.294 and 1.061, respectively, consistent with lymphedema. Furthermore, ICG lymphangiography in these cohort A rats revealed impaired lower limb lymphatic drainage. In cohort B, however, bioimpedance and circumference ratios, and ICG lymphangiography, did not reveal abnormal lymphatic drainage., Conclusions: The combination of inguinal lymphadenectomy, circumferential skin and subcutaneous tissue excision, and radiotherapy can successfully create lower limb lymphedema in the rat. When soft tissue excision is omitted, lymphedema does not develop.

Eugenol, a component of essential oils of medicinal and food plants, has a hypolipidemic effect in experimental animals although its mechanism of action is still unclear. This study aims to explore the mechanism of the hypolipidemic effect of eugenol in rats fed a high cholesterol and fat diet (HCFD). Eugenol significantly reduced total cholesterol (TC), low-density lipoproteins (LDL), atherogenic index (AI) but not high-density lipoproteins (HDL) or triglycerides (TG). Eugenol also decreased steatosis and hepatic inflammation in liver sections, decreased hepatomegaly, and the hepatic marker enzymes alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activity and increased the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activity in hypercholesterolemic rats. Eugenol did not inhibit hepatic 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase but caused down-regulation of transient receptor potential vanilloid (TRPV1) channels in the liver. Docking simulation using fast, rigid exhaustive docking (FRED) software indicated a tail-up/head-down interaction of eugenol with TRPV1 channel. Data indicate that eugenol does not inhibit HMG-CoA reductase but rather induces its action by interaction with TRPV1 channels.

A new series of thiazolo[3,2- a ]pyrimidine bromide salt derivatives 7a - d were synthesized from 3,4-dihydropyrimidinethione precursors. The target compounds were fully characterized by 1D- and 2D-NMR, high resolution ESI-MS/MS and single crystal X-ray diffraction analysis, which confirmed a regioselective 5 H cyclization of the dihydropyrimidinethiones. All target compounds were evaluated in vitro as human acetylcholinesterase ( h AChE) inhibitors via an Ellman-based colorimetric assay and showed good inhibition activities (better than 70% at 10 µM and IC 50 values in the 1 µM range). Molecular docking simulations for all target products into h AChE were performed and confirmed strong binding to the enzyme. These results provide a promising and new starting point to improve acetylcholinesterase inhibitors and explore novel treatment options against Alzheimer's disease.

Hypercholesterolemia is a major risk factor for cardiovascular diseases. This study investigated the cholesterol-lowering potential of β-caryophyllene in a rat model. Hypercholesterolemia was induced by feeding male Wistar rats a high cholesterol and fat diet for 2 weeks. This was followed by oral administration of β-caryophyllene to hypercholesterolemic rats at 30, 100 and 300 mg/kg b.w. for 4 weeks. A dose of 30 mg/kg of β-caryophyllene significantly lowered serum total cholesterol, low density lipoprotein and the atherogenic index and significantly increased high density lipoprotein level. Moreover, it ameliorated liver injury as evidenced by decreasing hepatomegaly, macrovesicular steatosis and the activity of hepatic marker enzymes alanine aminotransferase and aspartate aminotransferase. Furthermore, it increased the activity of the antioxidant enzyme superoxide dismutase. This dose of β-caryophyllene significantly inhibited the activity of hepatic hydroxy-methylglutaryl coenzyme A reductase. Higher doses (100 and 300 mg/kg) of β-caryophyllene, however, did not induce significant beneficial effects on the studied parameters. These observations demonstrate that β-caryophyllene has a cholesterol-lowering effect on hypercholesterolemic rats, thus offering protection against hypercholesterolemia-induced diseases such as atherosclerosis and fatty liver., Competing Interests: No potential conflicts of interest were disclosed.

Synthesis of 3,4-dihydropyrimidin-2(1H)-one and 3,4-dihydropyrimidin-2(1H)-thione derivatives from aldehydes, 1,3-dicarbonyl derivatives and urea or thiourea using granite and quartz as new, natural and reusable catalysts. Some of the 3,4-dihydropyrimidin-2(1H)-thione derivatives were used to prepare new heterocyclic compounds. The antimicrobial activity of selected examples of the synthesized compounds was tested and showed moderate activity.