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16 pages, 5893 KiB  
Article
Silibinin’s Effects against Methotrexate-Induced Hepatotoxicity in Adjuvant-Induced Arthritis Rat Model
by Ghada Khawaja and Youmna El-Orfali
Pharmaceuticals 2024, 17(4), 431; https://doi.org/10.3390/ph17040431 - 28 Mar 2024
Abstract
Methotrexate (MTX) is the first drug of choice to treat several diseases, including rheumatoid arthritis. However, its administration is accompanied by severe side effects, most commonly hepatotoxicity. Hence, alternative therapies with a lower toxicity and fewer side effects are needed. This study aimed [...] Read more.
Methotrexate (MTX) is the first drug of choice to treat several diseases, including rheumatoid arthritis. However, its administration is accompanied by severe side effects, most commonly hepatotoxicity. Hence, alternative therapies with a lower toxicity and fewer side effects are needed. This study aimed to investigate the antioxidant and hepatoprotective effects of silibinin (SIL, natural agent) against MTX-induced hepatotoxicity in an adjuvant-induced arthritis (AIA) rat model. Arthritic rats were treated with SIL (100 mg/kg) and/or methotrexate (2 mg/kg). Non-arthritic rats, arthritic untreated rats, and arthritic rats who received the vehicle were followed in parallel. SIL alleviated the systemic consequences of arthritis by restoring lost weight, decreasing the erythrocyte sedimentation rate, and ameliorating joint damage, which was evident both micro- and macroscopically. Additionally, SIL prevented the histopathological alterations in the liver and significantly reduced the liver damage caused by MTX and AIA, as shown by a decrease in the markers of liver damage (ALT and AST). Furthermore, SIL relieved the oxidative stress induced by AIA and MTX in liver tissue by decreasing the lipid peroxidation (MDA) levels and enhancing the antioxidant defense system (GSH levels; catalase and superoxide dismutase (SOD) activities). In conclusion, our results suggest that SIL is a potent antioxidant and hepatoprotective agent in arthritic rats. It markedly attenuated the progression and severity of the arthritic disease and eased the oxidative stress in liver tissue by improving the pro-oxidant/antioxidant balance. Full article
(This article belongs to the Special Issue Natural Products for the Treatment of Rheumatic Diseases)
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20 pages, 4477 KiB  
Article
An Application of a Physiologically Based Pharmacokinetic Approach to Predict Ceftazidime Pharmacokinetics in a Pregnant Population
by Khaled Abduljalil, Iain Gardner and Masoud Jamei
Pharmaceutics 2024, 16(4), 474; https://doi.org/10.3390/pharmaceutics16040474 - 28 Mar 2024
Abstract
Physiological changes during pregnancy can alter maternal and fetal drug exposure. The objective of this work was to predict maternal and umbilical ceftazidime pharmacokinetics during pregnancy. Ceftazidime transplacental permeability was predicted from its physicochemical properties and incorporated into the model. Predicted concentrations and [...] Read more.
Physiological changes during pregnancy can alter maternal and fetal drug exposure. The objective of this work was to predict maternal and umbilical ceftazidime pharmacokinetics during pregnancy. Ceftazidime transplacental permeability was predicted from its physicochemical properties and incorporated into the model. Predicted concentrations and parameters from the PBPK model were compared to the observed data. PBPK predicted ceftazidime concentrations in non-pregnant and pregnant subjects of different gestational weeks were within 2-fold of the observations, and the observed concentrations fell within the 5th–95th prediction interval from the PBPK simulations. The calculated transplacental clearance (0.00137 L/h/mL of placenta volume) predicted an average umbilical cord-to-maternal plasma ratio of 0.7 after the first dose, increasing to about 1.0 at a steady state, which also agrees well with clinical observations. The developed maternal PBPK model adequately predicted the observed exposure and kinetics of ceftazidime in the pregnant population. Using a verified population-based PBPK model provides valuable insights into the disposition of drug concentrations in special individuals that are otherwise difficult to study and, in addition, offers the possibility of supplementing sparse samples obtained in vulnerable populations with additional knowledge, informing the dosing adjustment and study design, and improving the efficacy and safety of drugs in target populations. Full article
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28 pages, 1842 KiB  
Review
Evaluation of Advanced Nanomaterials for Cancer Diagnosis and Treatment
by Nkanyiso L. Ndlovu, Wendy B. Mdlalose, Bulelwa Ntsendwana and Thomas Moyo
Pharmaceutics 2024, 16(4), 473; https://doi.org/10.3390/pharmaceutics16040473 - 28 Mar 2024
Abstract
Cancer is a persistent global disease and a threat to the human species, with numerous cases reported every year. Over recent decades, a steady but slowly increasing mortality rate has been observed. While many attempts have been made using conventional methods alone as [...] Read more.
Cancer is a persistent global disease and a threat to the human species, with numerous cases reported every year. Over recent decades, a steady but slowly increasing mortality rate has been observed. While many attempts have been made using conventional methods alone as a theragnostic strategy, they have yielded very little success. Most of the shortcomings of such conventional methods can be attributed to the high demands of industrial growth and ever-increasing environmental pollution. This requires some high-tech biomedical interventions and other solutions. Thus, researchers have been compelled to explore alternative methods. This has brought much attention to nanotechnology applications, specifically magnetic nanomaterials, as the sole or conjugated theragnostic methods. The exponential growth of nanomaterials with overlapping applications in various fields is due to their potential properties, which depend on the type of synthesis route used. Either top-down or bottom-up strategies synthesize various types of NPs. The top-down only branches out to one method, i.e., physical, and the bottom-up has two methods, chemical and biological syntheses. This review highlights some synthesis techniques, the types of nanoparticle properties each technique produces, and their potential use in the biomedical field, more specifically for cancer. Despite the evident drawbacks, the success achieved in furthering nanoparticle applications to more complex cancer stages and locations is unmatched. Full article
22 pages, 3341 KiB  
Article
Understanding the Interaction of Thermal, Rheological, and Mechanical Parameters Critical for the Processability of Polyvinyl Alcohol-Based Systems during Hot Melt Extrusion
by Florian Hess, Thomas Kipping, Werner Weitschies and Julius Krause
Pharmaceutics 2024, 16(4), 472; https://doi.org/10.3390/pharmaceutics16040472 - 28 Mar 2024
Abstract
Hot melt extrusion (HME) is a common manufacturing process used in the pharmaceutical industry to improve the solubility of poorly soluble active pharmaceutical ingredients (API). The goal is to create an amorphous solid dispersion (ASD) where the amorphous form of the API is [...] Read more.
Hot melt extrusion (HME) is a common manufacturing process used in the pharmaceutical industry to improve the solubility of poorly soluble active pharmaceutical ingredients (API). The goal is to create an amorphous solid dispersion (ASD) where the amorphous form of the API is stabilized within a polymer matrix. Traditionally, the development of pharmaceutically approved polymers has focused on requirements such as thermal properties, solubility, drug–polymer interactions, and biocompatibility. The mechanical properties of the material have often been neglected in the design of new polymers. However, new downstream methods require more flexible polymers or suitable plasticizer polymer combinations. In this study, two grades of the polymer polyvinyl alcohol (PVA), which is already established for HME, are investigated in terms of their mechanical, rheological, and thermal properties. The mechanical properties of the extruded filaments were tested by the three-point bending test. The rheological behavior was analyzed by oscillating plate measurements. Thermal analysis was performed by differential scanning calorimetry (DSC). In addition, the solid and liquid plasticizers mannitol, sorbitol, triacetin, triethyl citrate, polyethylene glycol, and glycerol were evaluated for use with PVA and their impact on the polymer properties was elaborated. Finally, the effects of the plasticizers are compared to each other, and the correlations are analyzed statistically using principal component analysis (PCA). Thereby, a clear ranking of the plasticizer effects was established, and a deeper understanding of the polymer–plasticizer interactions was created. Full article
(This article belongs to the Special Issue Impact of Raw Material Properties on Solid Dosage Form Processes)
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13 pages, 560 KiB  
Brief Report
Orthoflavivirus Lammi in Russia: Possible Transovarial Transmission and Trans-Stadial Survival in Aedes cinereus (Diptera, Culicidae)
by Ivan S. Kholodilov, Sergey V. Aibulatov, Alexei V. Khalin, Alexandra E. Polienko, Alexander S. Klimentov, Oxana A. Belova, Anastasiya A. Rogova, Sergey G. Medvedev and Galina G. Karganova
Viruses 2024, 16(4), 527; https://doi.org/10.3390/v16040527 - 28 Mar 2024
Abstract
In the last few years, there has been a dramatic increase in the number of discovered viruses that are transmitted by arthropods. Some of them are pathogenic for humans and mammals, and the pathogenic potential of others is unknown. The genus Orthoflavivirus belongs [...] Read more.
In the last few years, there has been a dramatic increase in the number of discovered viruses that are transmitted by arthropods. Some of them are pathogenic for humans and mammals, and the pathogenic potential of others is unknown. The genus Orthoflavivirus belongs to the family Flaviviridae and includes arboviruses that cause severe human diseases with damage to the central nervous system and hemorrhagic fevers, as well as viruses with unknown vectors and viruses specific only to insects. The latter group includes Lammi virus, first isolated from a mosquito pool in Finland. It is known that Lammi virus successfully replicates in mosquito cell lines but not in mammalian cell cultures or mice. Lammi virus reduces the reproduction of West Nile virus during superinfection and thus has the potential to reduce the spread of West Nile virus in areas where Lammi virus is already circulating. In this work, we isolated Lammi virus from a pool of adult Aedes cinereus mosquitoes that hatched from larvae/pupae collected in Saint Petersburg, Russia. This fact may indicate transovarial transmission and trans-stadial survival of the virus. Full article
(This article belongs to the Section Insect Viruses)
9 pages, 895 KiB  
Article
Hepatitis E Virus Infection in Voluntary Blood Donors in the Russian Federation
by Ilya A. Potemkin, Karen K. Kyuregyan, Anastasia A. Karlsen, Olga V. Isaeva, Vera S. Kichatova, Maria A. Lopatukhina, Fedor A. Asadi Mobarkhan, Anna G. Zlobina, Andrey V. Zheltobriukh, Ksenia A. Bocharova, Vera V. Belyakova, Svetlana V. Rassolova, Nadezhda V. Ivanova, Sergey A. Solonin, Alexey I. Bazhenov, Mikhail A. Godkov and Mikhail I. Mikhailov
Viruses 2024, 16(4), 526; https://doi.org/10.3390/v16040526 - 28 Mar 2024
Abstract
Transfusion-transmitted hepatitis E virus (HEV) infection is an increasing concern in many countries. We investigated the detection rate of HEV viremia in blood donors in Russia. A total of 20,405 regular repetitive voluntary non-renumerated blood donors from two regions (Moscow and Belgorod) were [...] Read more.
Transfusion-transmitted hepatitis E virus (HEV) infection is an increasing concern in many countries. We investigated the detection rate of HEV viremia in blood donors in Russia. A total of 20,405 regular repetitive voluntary non-renumerated blood donors from two regions (Moscow and Belgorod) were screened for HEV RNA using the cobas® HEV test in mini-pools of six plasma samples. Samples from each reactive pool were tested individually. The average HEV RNA prevalence was 0.024% (95% CI: 0.01–0.05%), or 1 case per 4081 donations. No statistically significant differences in HEV RNA prevalence were observed between the two study regions. The PCR threshold cycle (Ct) values ranged from 25.0 to 40.5 in reactive pools, and from 20.9 to 41.4 in reactive plasma samples when tested individually. The HEV viremic donors had different antibody patterns. Two donor samples were reactive for both anti-HEV IgM and IgG antibodies, one sample was reactive for anti-HEV IgM and negative for anti-HEV IgG, and two samples were seronegative. At follow-up testing 6 months later, on average, four donors available for follow-up had become negative for HEV RNA and positive for anti-HEV IgG. The HEV ORF2 sequence belonging to HEV-3 sub-genotype 3a was obtained from one donor sample. The sequencing failed in the other four samples from viremic donors, presumably due to the low viral load. In conclusion, the HEV RNA detection rate in blood donors in Russia corresponds with data from other European countries, including those that implemented universal donor HEV screening. These data support the implementation of HEV RNA donor screening to reduce the risk of transfusion-transmitted HEV infection in Russia. Full article
(This article belongs to the Special Issue Transfusion & Transplantation Transmitted Viral Infections)
13 pages, 2311 KiB  
Article
Mosquito E-20-Monooxygenase Gene Knockout Increases Dengue Virus Replication in Aedes aegypti Cells
by Bo Li, Di Wang, Xiaoxue Xie, Xiaoli Chen, Guorui Liang, Dan Xing, Teng Zhao, Jiahong Wu, Xinyu Zhou and Chunxiao Li
Viruses 2024, 16(4), 525; https://doi.org/10.3390/v16040525 - 28 Mar 2024
Abstract
E-20-monooxygenase (E20MO) is an enzymatic product of the shade (shd) locus (cytochrome p450, E20MO). Initially discovered in Drosophila, E20MO facilitates the conversion of ecdysone (E) into 20-hydroxyecdysone (20E) and is crucial for oogenesis. Prior research has implicated 20E in growth, development, and insecticide [...] Read more.
E-20-monooxygenase (E20MO) is an enzymatic product of the shade (shd) locus (cytochrome p450, E20MO). Initially discovered in Drosophila, E20MO facilitates the conversion of ecdysone (E) into 20-hydroxyecdysone (20E) and is crucial for oogenesis. Prior research has implicated 20E in growth, development, and insecticide resistance. However, little attention has been given to the association between the E20MO gene and DENV2 infection. The transcriptome of Ae. aegypti cells (Aag2 cells) infected with DENV2 revealed the presence of the E20MO gene. The subsequent quantification of E20MO gene expression levels in Aag2 cells post-DENV infection was carried out. A CRISPR/Cas9 system was utilized to create an E20MO gene knockout cell line (KO), which was then subjected to DENV infection. Analyses of DENV2 copies in KO and wild-type (WT) cells were conducted at different days post-infection (dpi). Plasmids containing E20MO were constructed and transfected into KO cells, with pre- and post-transfection viral copy comparisons. Gene expression levels of E20MO increased after DENV infection. Subsequently, a successful generation of an E20MO gene knockout cell line and the verification of code-shifting mutations at both DNA and RNA levels were achieved. Furthermore, significantly elevated DENV2 RNA copies were observed in the mid-infection phase for the KO cell line. Viral RNA copies were lower in cells transfected with plasmids containing E20MO, compared to KO cells. Through knockout and plasmid complementation experiments in Aag2 cells, the role of E20MO in controlling DENV2 replication was demonstrated. These findings contribute to our understanding of the intricate biological interactions between mosquitoes and arboviruses. Full article
(This article belongs to the Section Insect Viruses)
15 pages, 721 KiB  
Article
Dissemination of the Flavivirus Subgenomic Replicon Genome and Viral Proteins by Extracellular Vesicles
by Tomohiro Ishikawa, Kentaro Narita, Kinichi Matsuyama and Michiaki Masuda
Viruses 2024, 16(4), 524; https://doi.org/10.3390/v16040524 - 28 Mar 2024
Abstract
Extracellular vesicles (EVs) such as exosomes have been shown to play physiological roles in cell-to-cell communication by delivering various proteins and nucleic acids. In addition, several studies revealed that the EVs derived from the cells that are infected with certain viruses could transfer [...] Read more.
Extracellular vesicles (EVs) such as exosomes have been shown to play physiological roles in cell-to-cell communication by delivering various proteins and nucleic acids. In addition, several studies revealed that the EVs derived from the cells that are infected with certain viruses could transfer the full-length viral genomes, resulting in EVs-mediated virus propagation. However, the possibility cannot be excluded that the prepared EVs were contaminated with infectious viral particles. In this study, the cells that harbor subgenomic replicon derived from the Japanese encephalitis virus and dengue virus without producing any replication-competent viruses were employed as the EV donor. It was demonstrated that the EVs in the culture supernatants of those cells were able to transfer the replicon genome to other cells of various types. It was also shown that the EVs were incorporated by the recipient cells primarily through macropinocytosis after interaction with CD33 and Tim-1/Tim-4 on HeLa and K562 cells, respectively. Since the methods used in this study are free from contamination with infectious viral particles, it is unequivocally indicated that the flavivirus genome can be transferred by EVs from cell to cell, suggesting that this pathway, in addition to the classical receptor-mediated infection, may play some roles in the viral propagation and pathogenesis. Full article
(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)
17 pages, 1354 KiB  
Article
Novel Anti-Viral Properties of the Herbal Extract of Davallia mariesii against Influenza A Virus
by Yu-Li Chen, Pei-Yu Chao, Chung-Fan Hsieh, Pei-Wen Hsieh and Jim-Tong Horng
Viruses 2024, 16(4), 523; https://doi.org/10.3390/v16040523 - 28 Mar 2024
Abstract
Gu-Sui-Bu, the dried rhizome of Davallia mariesii, is a traditional Chinese herbal remedy with a significant history of treating osteoporosis and inflammatory conditions. However, its potential as an anti-influenza agent and its underlying mechanisms of action remain unexplored. To obtain a more [...] Read more.
Gu-Sui-Bu, the dried rhizome of Davallia mariesii, is a traditional Chinese herbal remedy with a significant history of treating osteoporosis and inflammatory conditions. However, its potential as an anti-influenza agent and its underlying mechanisms of action remain unexplored. To obtain a more potent extract from D. mariesii and gain insights into its mechanism of action against influenza A virus (IAV), we utilized a partitioning process involving organic solvents and water, resulting in the isolation of butanolic subfractions of the D. mariesii extract (DMBE). DMBE exhibited a broad anti-viral spectrum, effectively inhibiting IAV, with an EC50 of 24.32 ± 6.19 µg/mL and a selectivity index of 6.05. We subsequently conducted a series of in vitro assays to evaluate the antiviral effects of DMBE and to uncover its mechanisms of action. DMBE was found to inhibit IAV during the early stages of infection by hindering the attachment of the virus onto and its penetration into host cells. Importantly, DMBE was observed to hinder IAV-mediated cell–cell fusion. It also inhibited neuraminidase activity, plaque size, and the expression levels of phospho-AKT. In summary, this study provides evidence for the effectiveness of D. mariesii as a complementary and alternative herbal remedy against IAV. Specifically, our data highlight DMBE’s capabilities in inhibiting viral entry and the release of virions. Full article
(This article belongs to the Special Issue Novel and Repurposed Antiviral Agents, 2nd Edition)
14 pages, 1196 KiB  
Article
Peripheral Neuropathy in Patients with Hepatitis C Infection—Reversibility after HCV Eradication: A Single Center Study
by Theodoros Androutsakos, Ioanna Tsantzali, Dimitrios S. Karagiannakis, Pagona Flevari, Despoina Iakovou, Abraham Pouliakis, Stylianos Kykalos, Stylianos Doris and Vasileia Xyla
Viruses 2024, 16(4), 522; https://doi.org/10.3390/v16040522 - 28 Mar 2024
Abstract
Chronic hepatitis C virus (HCV) infection is characterized by a variety of extra-hepatic manifestations; peripheral neuropathy (PN) is one of the most common, especially when mixed cryoglobulinemia (MCG) is present. The prevalence and risk factors of HCV-related PN in the absence of MCG [...] Read more.
Chronic hepatitis C virus (HCV) infection is characterized by a variety of extra-hepatic manifestations; peripheral neuropathy (PN) is one of the most common, especially when mixed cryoglobulinemia (MCG) is present. The prevalence and risk factors of HCV-related PN in the absence of MCG are largely unknown. We conducted a prospective, single-center study, examining the prevalence and reversibility of HCV-associated neuropathy in the absence of MCG. Nerve fiber density in the epidermis was evaluated through skin biopsy and electroneurography (ENG) before HCV-treatment initiation and 1 year post sustained virological remission (SVR). Forty HCV-infected individuals (nine HIV co-infected) with no other neuron-harming factors were included; four other HCV mono- and three HIV co-infected individuals were excluded due to presence of diabetes, B12 insufficiency, or neurotoxic drugs. Twelve consecutive controls with no neuron-harming conditions were also recruited; eight more were excluded due to meeting exclusion criteria. Four patients had ENG signs of polyneuropathy (two with HCV mono- and two with HIV co-infection), while seven more (five with HCV mono- and two with HIV co-infection) had signs of mono-neuropathy, leading to PN prevalences of 22.5% and 44% for mono- and co-infection, respectively (p value 0.179). The two patients with HCV mono-infection and polyneuropathy and the one with ulnar nerve damage showed ENG improvement 1 year post SVR. Regarding intraepidermal nerve density, HCV infection, irrespective of HIV co-infection, was correlated with a lower intraepidermal neuron density that improved 1 year post SVR (p value 0.0002 for HCV and 0.0326 for HCV/HIV co-infected patients). PN is common in HCV infection; successful eradication of HCV leads to PN improvement. Full article
(This article belongs to the Special Issue Recent Advances in Anti-HCV, Anti-HBV and Anti-flavivirus Agents)
12 pages, 3122 KiB  
Article
Effects of Strain Differences, Humidity Changes, and Saliva Contamination on the Inactivation of SARS-CoV-2 by Ion Irradiation
by Afifah Fatimah Azzahra Ahmad Wadi, Daichi Onomura, Hirokazu Funamori, Mst Mahmuda Khatun, Shunpei Okada, Hisashi Iizasa and Hironori Yoshiyama
Viruses 2024, 16(4), 520; https://doi.org/10.3390/v16040520 - 28 Mar 2024
Abstract
One of the methods to inactivate viruses is to denature viral proteins using released ions. However, there have been no reports detailing the effects of changes in humidity or contamination with body fluids on the inactivation of viruses. This study investigated the effects [...] Read more.
One of the methods to inactivate viruses is to denature viral proteins using released ions. However, there have been no reports detailing the effects of changes in humidity or contamination with body fluids on the inactivation of viruses. This study investigated the effects of humidity changes and saliva contamination on the efficacy of SARS-CoV-2 inactivation with ions using multiple viral strains. Virus solutions with different infectious titers were dropped onto a circular nitrocellulose membrane and irradiated with ions from 10 cm above the membrane. After the irradiation of ions for 60, 90, and 120 min, changes in viral infectious titers were measured. The effect of ions on virus inactivation under different humidity conditions was also examined using virus solutions containing 90% mixtures of saliva collected from 10 people. A decrease in viral infectivity was observed over time for all strains, but ion irradiation further accelerated the decrease in viral infectivity. Ion irradiation can inactivate all viral strains, but at 80% humidity, the effect did not appear until 90 min after irradiation. The presence of saliva protected the virus from drying and maintained infectiousness for a longer period compared with no saliva. In particular, the Omicron strain retained its infectivity titer longer than the other strains. Ion irradiation demonstrated a consistent reduction in the number of infectious viruses when compared to the control across varying levels of humidity and irradiation periods. This underscores the notable effectiveness of irradiation, even when the reduction effect is as modest as 50%, thereby emphasizing its crucial role in mitigating the rapid dissemination of SARS-CoV-2. Full article
(This article belongs to the Special Issue Viruses 2024 - A World of Viruses)
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10 pages, 322 KiB  
Article
Detection of SARS-CoV-2 RNA in a Zoo-Kept Red Fox (Vulpes vulpes)
by Tatjana Chan, Julia Ginders, Evelyn Kuhlmeier, Marina L. Meli, Eva B?nzli, Theres Meili, Julia Hüttl, Jean-Michel Hatt, Karin Hindenlang Clerc, Anja Kipar, Fabia Wyss, Christian Wenker, Marie-Pierre Ryser-Degiorgis, Cecilia Valenzuela Agüí, Christian Urban, Christian Beisel, Tanja Stadler and Regina Hofmann-Lehmann
Viruses 2024, 16(4), 521; https://doi.org/10.3390/v16040521 - 28 Mar 2024
Abstract
Many different animal species are susceptible to SARS-CoV-2, including a few Canidae (domestic dog and raccoon dog). So far, only experimental evidence is available concerning SARS-CoV-2 infections in red foxes (Vulpes vulpes). This is the first report of SARS-CoV-2 RNA detection [...] Read more.
Many different animal species are susceptible to SARS-CoV-2, including a few Canidae (domestic dog and raccoon dog). So far, only experimental evidence is available concerning SARS-CoV-2 infections in red foxes (Vulpes vulpes). This is the first report of SARS-CoV-2 RNA detection in a sample from a red fox. The RT-qPCR-positive fox was zoo-kept together with another fox and two bears in the Swiss Canton of Zurich. Combined material from a conjunctival and nasal swab collected for canine distemper virus diagnostics tested positive for SARS-CoV-2 RNA with Ct values of 36.9 (E gene assay) and 35.7 (RdRp gene assay). The sample was analysed for SARS-CoV-2 within a research project testing residual routine diagnostic samples from different animal species submitted between spring 2020 and December 2022 to improve knowledge on SARS-CoV-2 infections within different animal species and investigate their potential role in a One Health context. Within this project, 246 samples from 153 different animals from Swiss zoos and other wild animal species all tested SARS-CoV-2 RT-qPCR and/or serologically negative so far, except for the reported fox. The source of SARS-CoV-2 in the fox is unknown. The fox disappeared within the naturally structured enclosure, and the cadaver was not found. No further control measures were undertaken. Full article
(This article belongs to the Section Animal Viruses)
15 pages, 3284 KiB  
Article
First Detection and Circulation of RHDV2 in New Zealand
by Robyn N. Hall, Katherine Trought, Tanja Strive, Janine A. Duckworth and Maria Jenckel
Viruses 2024, 16(4), 519; https://doi.org/10.3390/v16040519 - 28 Mar 2024
Abstract
Rabbit haemorrhage disease virus 2 (RHDV2) is a highly pathogenic lagovirus that causes lethal disease in rabbits and hares (lagomorphs). Since its first detection in Europe in 2010, RHDV2 has spread worldwide and has been detected in over 35 countries so far. Here, [...] Read more.
Rabbit haemorrhage disease virus 2 (RHDV2) is a highly pathogenic lagovirus that causes lethal disease in rabbits and hares (lagomorphs). Since its first detection in Europe in 2010, RHDV2 has spread worldwide and has been detected in over 35 countries so far. Here, we provide the first detailed report of the detection and subsequent circulation of RHDV2 in New Zealand. RHDV2 was first detected in New Zealand in 2018, with positive samples retrospectively identified in December 2017. Subsequent time-resolved phylogenetic analysis suggested a single introduction into the North Island between March and November 2016. Genetic analysis identified a GI.3P-GI.2 variant supporting a non-Australian origin for the incursion; however, more accurate identification of the source of the incursion remains challenging due to the wide global distribution of the GI.3P-GI.2 variant. Furthermore, our analysis suggests the spread of the virus between the North and South Islands of New Zealand at least twice, dated to mid-2017 and around 2018. Further phylogenetic analysis also revealed a strong phylogeographic pattern. So far, no recombination events with endemic benign New Zealand rabbit caliciviruses have been identified. This study highlights the need for further research and surveillance to monitor the distribution and diversity of lagoviruses in New Zealand and to detect incursions of novel variants. Full article
(This article belongs to the Special Issue Rabbit Viral Diseases)
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11 pages, 332 KiB  
Article
Bullying at School, Cyberbullying, and Loneliness: National Representative Study of Adolescents in Denmark
by Katrine Rich Madsen, Mogens Trab Damsgaard, Kimberly Petersen, Pamela Qualter and Bj?rn E. Holstein
Int. J. Environ. Res. Public Health 2024, 21(4), 414; https://doi.org/10.3390/ijerph21040414 - 28 Mar 2024
Abstract
Aims: The aim was to examine how loneliness was associated with bullying victimization at school and online. Methods: We used data from the Danish arm of the international Health Behavior in School-aged Children (HBSC) study from 2022. The study population was a nationally [...] Read more.
Aims: The aim was to examine how loneliness was associated with bullying victimization at school and online. Methods: We used data from the Danish arm of the international Health Behavior in School-aged Children (HBSC) study from 2022. The study population was a nationally representative sample of 11–15-year-olds who completed the internationally standardized HBSC questionnaire at school, n = 5382. Multilevel logistic regression was applied to study the associations between bullying victimization and loneliness. Results: The prevalence of reporting loneliness often or very often was 9.0%; 6.3% of the sample experienced habitual bullying victimization at school, and 4.8% incurred cyberbullying. There was a strong and graded association between loneliness and bullying victimization at school and cyberbullying. The associations were significant for boys and girls, and the association between exposure to bullying at school and loneliness was steeper for boys than girls. The gradients were steeper for physical bullying than for cyberbullying. Students exposed to habitual bullying in both contexts had an adjusted OR (95% CI) of 11.21 (6.99–17.98) for loneliness. Conclusion: Exposure to bullying at school and cyberbullying are strongly associated with loneliness. It is important to reduce bullying at school and on the internet and to promote effective interventions to reduce continuing loneliness. Full article
11 pages, 447 KiB  
Article
A Community-Based Prostate Cancer Screening and Education Program for Asian American Men in Medically Underserved Communities
by Dalnim Cho, Beverly Gor, Hyunsoo Hwang, Xuemei Wang, Mike Hernandez, Lovell A. Jones, Jacqueline Frost, Pamela Roberson and Curtis A. Pettaway
Int. J. Environ. Res. Public Health 2024, 21(4), 415; https://doi.org/10.3390/ijerph21040415 - 28 Mar 2024
Abstract
This study analyzed data from a community-based prostate cancer (PCa) education and screening program (Prostate Outreach Project; POP) to enhance PCa-related knowledge among medically underserved Asian American men. It also examined PCa screening history, clinical abnormalities based on prostate-specific antigen (PSA) tests and [...] Read more.
This study analyzed data from a community-based prostate cancer (PCa) education and screening program (Prostate Outreach Project; POP) to enhance PCa-related knowledge among medically underserved Asian American men. It also examined PCa screening history, clinical abnormalities based on prostate-specific antigen (PSA) tests and digital rectal examination (DRE) results, and follow-up and PCa diagnosis rates. Participants—521 Asian men (251 Vietnamese, 142 Chinese, and 128 South Asians)—were offered PCa screening using PSA tests and/or DRE and an educational session on PCa. Of these men, 277 completed PCa-related knowledge surveys before and after viewing an educational video. Significant between-group differences in PCa-related knowledge were found at pre-assessment (p < 0.001) but not at post-assessment (p = 0.11), at which time all groups showed improved PCa-related knowledge. Most participants (77.9%) had never received PCa screening, but Vietnamese men had the lowest previous screening rate (17.3%). Chinese men had elevated PSA values and the highest abnormal DRE rates. Of the 125 men with abnormal screening outcomes, only 15.2% had adequate follow-up. Of the 144 men diagnosed with PCa in POP, 11.1% were Asians (seven Chinese, six Vietnamese, and three South Asian). Despite the ethnic heterogeneity among Asian men, a community outreach program may successfully enhance their PCa-related knowledge. Full article
22 pages, 539 KiB  
Systematic Review
Natural Environments in University Campuses and Students’ Well-Being
by Helena Ribeiro, Keila Valente de Souza Santana and Sofia Lizarralde Oliver
Int. J. Environ. Res. Public Health 2024, 21(4), 413; https://doi.org/10.3390/ijerph21040413 - 28 Mar 2024
Abstract
Most recent university campuses follow the North American model, built on city limits or countryside, with large separate buildings in open green spaces. Studies suggest that the prevalence and severity of mental health issues among university students has been increasing over the past [...] Read more.
Most recent university campuses follow the North American model, built on city limits or countryside, with large separate buildings in open green spaces. Studies suggest that the prevalence and severity of mental health issues among university students has been increasing over the past decade in most countries. University services were created to face this growing problem, however individual-based interventions have limited effects on mental health and well-being of a large population. Our aim was to verify if and how the natural environment in campuses is focused on programs to cope with the issue of mental health and well-being among students. A systematic review of literature was undertaken with search in Scopus and LILACS with the keywords “green areas” AND “well-being” AND “Campus”, following PRISMA guidelines. As a result, 32 articles were selected. Research on the topic is recent, mostly in the USA, Bulgaria, and China. Most studies used objective information on campuses’ greenness and/or university students’ perception. Mental health was usually measured by validated scores. Findings of all the studies indicated positive association between campus greenery and well-being of students. We conclude that there is a large potential for use of university campuses in programs and as sites for students’ restoration and stress relief. Full article
(This article belongs to the Special Issue Effects of Natural Environments on Human Well-Being)
11 pages, 4523 KiB  
Article
Association of Food Desert Residency and Preterm Birth in the United States
by Chanell O. Haley, Chelsea R. Singleton, Lily E. King, Lauren Dyer, Katherine P. Theall and Maeve Wallace
Int. J. Environ. Res. Public Health 2024, 21(4), 412; https://doi.org/10.3390/ijerph21040412 - 28 Mar 2024
Abstract
Introduction: Food deserts are a major public health concern. Inadequate access to healthy food has been associated with poor nutrition and the development of dietary related chronic conditions. Objective: To determine the association between geographic access to nutritious food and preterm birth and [...] Read more.
Introduction: Food deserts are a major public health concern. Inadequate access to healthy food has been associated with poor nutrition and the development of dietary related chronic conditions. Objective: To determine the association between geographic access to nutritious food and preterm birth and whether gestational hypertension mediates this relationship. Methods: Food access data was retrieved from the U.S. Department of Agriculture Food Access Research Atlas (2019) and used to quantify the percentage of Census tracts within each county that were food deserts: low-income tracts with limited access to grocery stores, supermarkets, or other sources of healthy, nutritious foods. These data were merged with US birth records from 2018 to 2019 by using the maternal county of residence (n = 7,533,319). We fit crude and adjusted logistic regression models with generalized estimating equations to determine the association between living in a food desert and the odds of preterm birth. We conducted a secondary within-group analysis by stratifying the fully adjusted model by race for non-Hispanic White and non-Hispanic Black birthing people. Results: In the fully adjusted model, we found a dose–response relationship. As the prevalence of tract-level food deserts within counties increased, so did the likelihood of preterm birth (mid-range: odds ratio (OR) = 1.04, 95% confidence interval (C.I.) 1.01–1.07; high: OR = 1.07, 95% C.I. 1.03–1.11). Similar results were seen in the White–Black stratified models. However, a disparity remained as Black birthing people had the highest odds for preterm birth. Lastly, gestational hypertension appears to mediate the relationship between nutritious food access and preterm birth (natural indirect effect (NIE) = 1.01, 95% CI = 1.00, 1.01). Conclusion: It is salient, particularly for Black birthing people who experience high rates of adverse birth outcomes, that the role of food desert residency be explored within maternal and child health disparities. Full article
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23 pages, 2116 KiB  
Systematic Review
Effectiveness of Point of Entry Health Screening Measures among Travelers in the Detection and Containment of the International Spread of COVID-19: A Review of the Evidence
by Remidius Kamuhabwa Kakulu, Esther Gwae Kimaro and Emmanuel Abraham Mpolya
Int. J. Environ. Res. Public Health 2024, 21(4), 410; https://doi.org/10.3390/ijerph21040410 - 28 Mar 2024
Abstract
COVID-19 remains a communicable disease with the capacity to cause substantial damage to health and health systems. Enhanced health screening at points of entry (POEs) is a public health measure implemented to support early detection, prevention and response to communicable diseases, such as [...] Read more.
COVID-19 remains a communicable disease with the capacity to cause substantial damage to health and health systems. Enhanced health screening at points of entry (POEs) is a public health measure implemented to support early detection, prevention and response to communicable diseases, such as COVID-19. The purpose of this study was to review the available evidence on the effectiveness of POE health screening in the detection and containment of the COVID-19 pandemic. This study was registered under PROSPERO and followed PRISMA guidelines in which the literature between 2019 and 2022 was retrieved from Scopus, PubMed, Web of Science, Global Health, CINAHL, Embase, Google Scholar and international organizations. A total of 33,744 articles were screened for eligibility, from which 43 met the inclusion criteria. The modeling studies predicted POE screening able to detect COVID-19 in a range of 8.8% to 99.6%, while observational studies indicated a detection rate of 2% to 77.9%, including variants of concern depending on the screening method employed. The literature also indicated these measures can delay onset of the epidemic by 7 to 32 days. Based on our review findings, if POE screening measures are implemented in combination with other public health interventions such as rapid tests, they may help detect and reduce the spread of COVID-19. Full article
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10 pages, 313 KiB  
Review
A Settings and Systems Approach to Promoting the Health and Wellbeing of People with an Intellectual Disability
by Andrew Joyce
Int. J. Environ. Res. Public Health 2024, 21(4), 409; https://doi.org/10.3390/ijerph21040409 - 28 Mar 2024
Abstract
Research has shown that people with an intellectual disability have higher rates of certain preventable health conditions and a higher rate of avoidable mortality relative to the general population. With respect to health behaviours, they also have lower levels of physical activity and [...] Read more.
Research has shown that people with an intellectual disability have higher rates of certain preventable health conditions and a higher rate of avoidable mortality relative to the general population. With respect to health behaviours, they also have lower levels of physical activity and poorer nutrition. Despite the increased health needs, this population cohort is less likely to have the opportunity to participate in health promotion programs. The interventions that have been delivered are programmatic and individual in focus and have lacked a broader ecological and settings focus, which makes them very difficult to scale. Health promotion programs designed for the general population, such as lifestyle campaigns, rarely reach people with an intellectual disability. This increases the importance of ensuring that the settings in which they live and engage with are as health promoting as possible. Interventions have been particularly absent in the workplace for people with an intellectual disability. This paper highlights gaps in a settings-and-systems-based approach to promoting the health and wellbeing of people with an intellectual disability, particularly with respect to workplace health promotion. The paper concludes with recommendations for a systems approach that integrates approaches across multiple settings to better promote the health of this population cohort. Full article
26 pages, 6716 KiB  
Article
Investigation of Underlying Association between Anthropometric and Cardiorespiratory Fitness Markers among Overweight and Obese Adolescents in Canada
by Mario Leone, Hung Tien Bui, Emilia Kalinova, Jean Lemoyne, Dominic Gagnon, Luc Léger, Georges Larivière and Maxime Allisse
Int. J. Environ. Res. Public Health 2024, 21(4), 408; https://doi.org/10.3390/ijerph21040408 - 28 Mar 2024
Abstract
Background: Adolescents who experience overweight or obesity commonly persist in these conditions into adulthood, thereby elevating their vulnerability to health issues. The focus of this study is on health risk markers such as body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), [...] Read more.
Background: Adolescents who experience overweight or obesity commonly persist in these conditions into adulthood, thereby elevating their vulnerability to health issues. The focus of this study is on health risk markers such as body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), body surface area (BSA), and cardiorespiratory fitness (CRF). The objectives include updating normative values for BMI, WC, WHtR, and BSA in Canadian adolescents, establishing cardiometabolic risk zones, and developing a composite score considering both anthropometric and CRF markers. Methods: Involving 1864 adolescents, the study used the LMS method to generate percentile norms, stratified by age and sex. Cardiometabolic risk zones were established for each marker based on Z-scores, and a composite score was created. Results: An increase in WC of 5.8 and 7.4 cm for boys and girls, respectively, was observed since 1981. Forward multiple regression analyses were conducted to assess the robustness and validity of the proposed model. The results indicated that the model explained nearly 90% (R2 = 0.890) of the common variance between the composite score and the retained independent variables. Moreover, the model demonstrated a mean absolute error (MAE) of approximately 6 percentiles, confirming its high precision. Furthermore, these analyses yielded key thresholds for identifying adolescents at risk: the 70th percentile for high cardiometabolic risk and the 85th percentile for very-high risk. Conclusions: Individually, WC or WHtR seem to be better markers for evaluating cardiometabolic risk than BMI during adolescence. However, CRF showed comparable importance to anthropometric markers in determining cardiometabolic risk. The simultaneous inclusion of anthropometric and CRF markers provides a better picture of the global cardiometabolic risk in adolescents. Full article
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24 pages, 884 KiB  
Systematic Review
A Systematic Umbrella Review of the Effects of Teledentistry on Costs and Oral-Health Outcomes
by Janneke F. M. Scheerman, Alaa H. Qari, Benoit Varenne, Harmen Bijwaard, Laura Swinckels, Nicolas Giraudeau, Berno van Meijel and Rodrigo Mari?o
Int. J. Environ. Res. Public Health 2024, 21(4), 407; https://doi.org/10.3390/ijerph21040407 - 28 Mar 2024
Abstract
Teledentistry offers possibilities for improving efficiency and quality of care and supporting cost-effective healthcare systems. This umbrella review aims to synthesize existing systematic reviews on teledentistry and provide a summary of evidence of its clinical- and cost-effectiveness. A comprehensive search strategy involving various [...] Read more.
Teledentistry offers possibilities for improving efficiency and quality of care and supporting cost-effective healthcare systems. This umbrella review aims to synthesize existing systematic reviews on teledentistry and provide a summary of evidence of its clinical- and cost-effectiveness. A comprehensive search strategy involving various teledentistry-related terms, across seven databases, was conducted. Articles published until 24 April 2023 were considered. Two researchers independently reviewed titles, abstracts and full-text articles. The quality of the included reviews was critically appraised with the AMSTAR-2 checklist. Out of 749 studies identified, 10 were included in this umbrella review. Two reviews focusing on oral-health outcomes revealed that, despite positive findings, there is not yet enough evidence for the long-term clinical effectiveness of teledentistry. Ten reviews reported on economic evaluations or costs, indicating that teledentistry is cost-saving. However, these conclusions were based on assumptions due to insufficient evidence on cost-effectiveness. The main limitation of our umbrella review was the critically low quality of the included reviews according to AMSTAR-2 criteria, with many of these reviews basing their conclusions on low-quality studies. This highlights the need for high-quality experimental studies (e.g., RCTs, factorial designs, stepped-wedge designs, SMARTs and MRTs) to assess teledentistry’s clinical- and cost-effectiveness. Full article
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16 pages, 3909 KiB  
Article
Anti-Inflammatory Effects of a Novel Acetonitrile–Water Extract of Lens Culinaris against LPS-Induced Damage in Caco-2 Cells
by Fatima Maqoud, Antonella Orlando, Domenico Tricarico, Marina Antonacci, Annamaria Di Turi, Gianluigi Giannelli and Francesco Russo
Int. J. Mol. Sci. 2024, 25(7), 3802; https://doi.org/10.3390/ijms25073802 - 28 Mar 2024
Abstract
Natural compounds like flavonoids preserve intestinal mucosal integrity through their antioxidant, anti-inflammatory, and antimicrobial properties. Additionally, some flavonoids show prebiotic abilities, promoting the growth and activity of beneficial gut bacteria. This study investigates the protective impact of Lens culinaris extract (LE), which is [...] Read more.
Natural compounds like flavonoids preserve intestinal mucosal integrity through their antioxidant, anti-inflammatory, and antimicrobial properties. Additionally, some flavonoids show prebiotic abilities, promoting the growth and activity of beneficial gut bacteria. This study investigates the protective impact of Lens culinaris extract (LE), which is abundant in flavonoids, on intestinal mucosal integrity during LPS-induced inflammation. Using Caco-2 cells as a model for the intestinal barrier, the study found that LE did not affect cell viability but played a cytoprotective role in the presence of LPS. LE improved transepithelial electrical resistance (TEER) and tight junction (TJ) protein levels, which are crucial for barrier integrity. It also countered the upregulation of pro-inflammatory genes TRPA1 and TRPV1 induced by LPS and reduced pro-inflammatory markers like TNF-α, NF-κB, IL-1β, and IL-8. Moreover, LE reversed the LPS-induced upregulation of AQP8 and TLR-4 expression. These findings emphasize the potential of natural compounds like LE to regulate the intestinal barrier and reduce inflammation’s harmful effects on intestinal cells. More research is required to understand their mechanisms and explore therapeutic applications, especially for gastrointestinal inflammatory conditions. Full article
(This article belongs to the Section Molecular Immunology)
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17 pages, 1305 KiB  
Article
Pelvic Organ Prolapse Reconstruction with the Chitosan-Based Novel Haemostatic Agent in Ovine Model—Preliminary Report
by Klaudia Stangel-Wójcikiewicz, Maciej Murawski, Tomasz Schwarz, Krzysztof Skotniczny, Agnieszka Fuchs, Jan Wolski, Julia Radwan-Prag?owska, ?ukasz Janus, Marek Pi?tkowski, Marta Kot, Andrzej Wróbel, Dorota Wojtysiak and Przemys?aw Urbaniec
Int. J. Mol. Sci. 2024, 25(7), 3801; https://doi.org/10.3390/ijms25073801 - 28 Mar 2024
Abstract
This prospective study aimed to assess the feasibility of chitosan biomaterial and subcutaneous gel implantation in an ovine model, with implications for women with genital prolapse. Twenty-four ewes were divided into four groups (n = 6 per group): chitosan type B, chitosan type [...] Read more.
This prospective study aimed to assess the feasibility of chitosan biomaterial and subcutaneous gel implantation in an ovine model, with implications for women with genital prolapse. Twenty-four ewes were divided into four groups (n = 6 per group): chitosan type B, chitosan type C, chitosan unmodified injections, and polypropylene mesh. Ovine models were chosen due to their morphological resemblance to human reproductive organs. Animals were sacrificed after 90 days for macroscopic, pathomorphological, and immunohistochemical analysis. In the chitosan type B group, IL-6 and IL-10 levels decreased after 28 days, while chitosan type C and injection groups exhibited higher IL-6 than IL-10 levels. The polypropylene group displayed the highest IL-6 and lowest IL-10 levels. Histological examination of the polypropylene group revealed no degenerative changes or inflammation, whereas chitosan injection induced local inflammation. Other groups exhibited no degenerative changes. Ewes implanted with chitosan displayed reduced inflammation compared to polypropylene-implanted ewes. Chitosan implantation facilitated vaginal tissue healing, in contrast to polypropylene mesh, which led to extrusion. While chitosan holds promise as an alternative to polypropylene mesh, further research is imperative for comprehensive evaluation. This study suggests the potential of a chitosan biomaterial in pelvic organ prolapse treatment, warranting additional investigation. Full article
(This article belongs to the Section Materials Science)

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