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20 pages, 2783 KiB  
Article
Dietary Tea Polyphenols Improve Growth Performance and Intestinal Microbiota Under Chronic Crowding Stress in Hybrid Crucian Carp
by Zhe Yang, Gege Sun, Jinsheng Tao, Weirong Tang, Wenpei Li, Zehong Wei and Qifang Yu
Animals 2025, 15(13), 1983; https://doi.org/10.3390/ani15131983 - 5 Jul 2025
Viewed by 368
Abstract
This study systematically investigated the effects of dietary tea polyphenols (TPs, major bioactive polyphenols from Camellia sinensis with potent antioxidant and anti-inflammatory properties) on the growth performance and intestinal health of hybrid crucian carp HCC2 under chronic crowding stress. A low-density control group [...] Read more.
This study systematically investigated the effects of dietary tea polyphenols (TPs, major bioactive polyphenols from Camellia sinensis with potent antioxidant and anti-inflammatory properties) on the growth performance and intestinal health of hybrid crucian carp HCC2 under chronic crowding stress. A low-density control group (44.4 fish/m3, basal diet without TPs) and four high-density crowding stress groups (222.2 fish/m3) were established, one fed the basal diet without TPs (CS) and three fed basal diets supplemented with 100 (CSLTP), 200 (CSMTP), or 400 (CSHTP) mg/kg TPs. We analyzed the impacts of TPs on growth performance, serum biochemical parameters, antioxidant capacity, expression of lipid metabolism-related genes, and intestinal microbiota composition. The results demonstrated that chronic crowding stress significantly suppressed the final body weight, weight gain rate, and specific growth rate of HCC2, while increasing serum lactate LDH, TG, and ALB and decreasing GLU, LDL-C, ALT, AST, and ALP levels. Dietary TPs supplementation enhanced antioxidant capacity (T-AOC, SOD, CAT, and GSH) and alleviated lipid metabolic disorders by activating the Nrf2/Keap1 and PPARα signaling pathways, thereby upregulating the expression of liver antioxidant genes (CAT and SOD) and fatty acid oxidation genes (CPT1 and acox1). Furthermore, intestinal microbiota analysis revealed that chronic crowding stress significantly increased the abundance of Proteobacteria and decreased the proportion of Firmicutes compared to the low-density control. Dietary TPs intervention, particularly at higher doses, partially restored the Firmicutes abundance and reduced the enrichment of potential pathogenic bacteria associated with stress. This study is the first to comprehensively elucidate the mechanism by which TPs alleviate crowding stress through enhanced antioxidant capacity, metabolic regulation, and microbiota remodeling, providing robust theoretical support for the application of plant-based additives in aquaculture. Full article
(This article belongs to the Section Aquatic Animals)
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15 pages, 2660 KiB  
Article
Role of Vaccination Strategies to Host-Pathogen Dynamics in Social Interactions
by Marlon Nunes Gonzaga, Marcelo Martins de Oliveira and Allbens Picardi Faria Atman
Entropy 2024, 26(9), 739; https://doi.org/10.3390/e26090739 - 30 Aug 2024
Viewed by 1145
Abstract
This study presents extended Immunity Agent-Based Model (IABM) simulations to evaluate vaccination strategies in controlling the spread of infectious diseases. The application of IABM in the analysis of vaccination configurations is innovative, as a vaccinated individual can be infected depending on how their [...] Read more.
This study presents extended Immunity Agent-Based Model (IABM) simulations to evaluate vaccination strategies in controlling the spread of infectious diseases. The application of IABM in the analysis of vaccination configurations is innovative, as a vaccinated individual can be infected depending on how their immune system acts against the invading pathogen, without a pre-established infection rate. Analysis at the microscopic level demonstrates the impact of vaccination on individual immune responses and infection outcomes, providing a more realistic representation of how the humoral response caused by vaccination affects the individual’s immune defense. At the macroscopic level, the effects of different population-wide vaccination strategies are explored, including random vaccination, targeted vaccination of specific demographic groups, and spatially focused vaccination. The results indicate that increased vaccination rates are correlated with decreased infection and mortality rates, highlighting the importance of achieving herd immunity. Furthermore, strategies focused on vulnerable populations or densely populated regions prove to be more effective in reducing disease transmission compared to randomly distributed vaccination. The results presented in this work show that vaccination strategies focused on highly crowded regions are more efficient in controlling epidemics and outbreaks. Results suggest that applying vaccination only in the densest region resulted in the suppression of infection in that region, with less intense viral spread in areas with lower population densities. Strategies focused on specific regions, in addition to being more efficient in reducing the number of infected and dead people, reduce costs related to transportation, storage, and distribution of doses compared to the random vaccination strategy. Considering that, despite scientific efforts to consolidate the use of mass vaccination, the accessibility, affordability, and acceptability of vaccines are problems that persist, investing in the study of strategies that mitigate such issues is crucial in the development and application of government policies that make immunization systems more efficient and robust. Full article
(This article belongs to the Special Issue Modeling and Control of Epidemic Spreading in Complex Societies)
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16 pages, 3626 KiB  
Article
Case of Vibrio vulnificus Infection in Orechromis niloticus during Suspension of Recirculating Aquaculture System
by Yan Cai, Liu Jiang, Shaoqun Wang, Zhangding Zhao, Yongcan Zhou and Shifeng Wang
Water 2024, 16(13), 1878; https://doi.org/10.3390/w16131878 - 30 Jun 2024
Cited by 1 | Viewed by 2256
Abstract
During a suspension of a GIFT tilapia broodstock recirculating aquaculture system (RAS), a significant fish mortality event occurred. To determine the cause, four bacterial strains were isolated from affected fish and identified as Vibrio vulnificus through 16S rDNA sequencing. Virulence assays confirmed the [...] Read more.
During a suspension of a GIFT tilapia broodstock recirculating aquaculture system (RAS), a significant fish mortality event occurred. To determine the cause, four bacterial strains were isolated from affected fish and identified as Vibrio vulnificus through 16S rDNA sequencing. Virulence assays confirmed the pathogenicity of these strains, with the most virulent, CS-4, selected for a further analysis. Antimicrobial testing revealed CS-4’s sensitivity to 19 antibiotics, including meloxicillin and Gentamicin. Challenge tests indicated varied 7-day Lethal Dose 50 (LD50) values for CS-4 depending on the infection route, with immersion after skin injury being the most lethal. Additionally, the effects of salinity, crowding with air exposure, and nitrite on tilapia mortality were evaluated. The results showed that salinity stress increased the mortality rate of tilapia infected with V. vulnificus through immersion, and that salinity stress and V. vulnificus infection had a synergistic effect. A 20 min crowding with air exposure stress reduced the mortality rate of Nile tilapia infected with V. vulnificus. Nitrite stress had little effect on the mortality rate of tilapia infected with V. vulnificus. The results of the risk factor analysis indicated that salinity was the main factor affecting tilapia mortality caused by V. vulnificus infection. This study will serve as a valuable reference for the future management of similar RAS. Full article
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16 pages, 1358 KiB  
Review
Comprehensive Review of Tinea Capitis in Adults: Epidemiology, Risk Factors, Clinical Presentations, and Management
by Rachel C. Hill, Jeremy A. W. Gold and Shari R. Lipner
J. Fungi 2024, 10(5), 357; https://doi.org/10.3390/jof10050357 - 16 May 2024
Cited by 9 | Viewed by 10377
Abstract
Tinea capitis is a fungal infection of the scalp and hair caused by dermatophyte molds, that most often affects children and may also affect adults. Previous estimates suggest that between 3% and 11% of all tinea capitis cases worldwide occur in adults, although [...] Read more.
Tinea capitis is a fungal infection of the scalp and hair caused by dermatophyte molds, that most often affects children and may also affect adults. Previous estimates suggest that between 3% and 11% of all tinea capitis cases worldwide occur in adults, although updated epidemiological studies are needed to reassess the prevalence of tinea capitis in adult populations specifically. Postmenopausal adult women are most often affected by tinea capitis, with African American or Black women particularly at risk. Adults who experience crowded living conditions, who live in close proximity to animals, who are immunosuppressed, and/or who live in households with affected children are at greatest risk of infection. Tinea capitis can be non-inflammatory or inflammatory in nature, and the subtype affects the extent and severity of clinical symptoms. Fungal culture and potassium hydroxide preparations are the most commonly used diagnostic tools. Trichoscopy, defined as dermoscopic imaging of the scalp and hair, is a useful adjunct to the physical examination. The mainstay of therapy is oral antifungal therapy, and topical therapy alone is not recommended. Since tinea capitis infection is uncommon in adults, there are no widely accepted treatment guidelines. Rather, the same medications used for tinea capitis infection among children are recommended for adults at varying doses, including griseofulvin, and terbinafine, and, less commonly, itraconazole and fluconazole. The prognosis for tinea capitis in adults is typically excellent when prompt and adequate treatment is administered; however, delayed diagnosis or inadequate treatment can result in scarring alopecia. Over the past decade, dermatophyte infections resistant to treatment with topical and oral antifungal agents have emerged. While tinea capitis infections resistant to antifungal therapy have been rarely reported to date, antifungal resistance is rising among superficial fungal infections in general, and antifungal stewardship is necessary to ensure that resistance to treatment does not develop among dermatophytes that cause tinea capitis. Full article
(This article belongs to the Special Issue Hot Topics in Superficial Fungal Infections, 2nd Edition)
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13 pages, 2407 KiB  
Article
Equitable Vaccine Access in Light of COVID-19 Vaccine Procurement Strategies in Africa
by George L. O’Hara, Sam Halabi and Olohikhuae Egbokhare
COVID 2024, 4(2), 276-288; https://doi.org/10.3390/covid4020019 - 17 Feb 2024
Cited by 1 | Viewed by 2309
Abstract
(1) Background: This study addresses two weaknesses in current international efforts to prevent and prepare for the next pandemic: the lack of robust evidence supporting global policy measures and the corresponding extent to which those measures advance equity. (2) Methods: Using UNICEF’s publicly [...] Read more.
(1) Background: This study addresses two weaknesses in current international efforts to prevent and prepare for the next pandemic: the lack of robust evidence supporting global policy measures and the corresponding extent to which those measures advance equity. (2) Methods: Using UNICEF’s publicly available but underused COVID-19 Market Dashboard database, we conducted a cross-sectional analysis of vaccine deliveries as of mid-2022 and vaccine procurement strategies used by African low- and lower middle-income countries (LMICs) over the course of the COVID-19 pandemic. (3) Results: Pooled procurement of the kind typified by COVAX (a clearinghouse for high-income-country contributions of vaccines and financing toward the end of equitable LMIC procurement) crowded out alternative strategies that must be supported in future: regional procurement, donation, and bilateral procurement (binding agreement between two parties: one seller (i.e., a national government or a vaccine manufacturer) and one recipient (i.e., national government)), which showed a significant relationship with technology transfer and advancing local production capacity. (4) Conclusions: Expanding the scope of vaccine procurement alternatives to COVAX such as regional pooled procurement and bilateral procurement can stratify risk of supply agreements not materializing in actual supply. Sharing the technology necessary to produce vaccines with LMICs can mitigate obstacles to bilateral procurement. A pooled purchase alliance to procure vaccine doses on behalf of participating countries within a given region can benefit LMICs by accounting for infrastructure limitations that these countries share. Finally, donations bolster global redistributed supply essential to LMICs. Full article
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15 pages, 1200 KiB  
Article
Effect of Total Dose Irradiation on Parasitic BJT in 130 nm PDSOI MOSFETs
by Yupeng Jia, Zhengxuan Zhang, Dawei Bi, Zhiyuan Hu and Shichang Zou
Micromachines 2023, 14(9), 1679; https://doi.org/10.3390/mi14091679 - 28 Aug 2023
Cited by 1 | Viewed by 1661
Abstract
In this work, the effects of total dose irradiation on the parasitic bipolar junction transistor (BTJ) in 130 nm PDSOI MOSFETs were investigated. The experimental results demonstrate that irradiation-induced oxide-trap charges can modify the E-B junction barrier, and thereby make the common-emitter gain [...] Read more.
In this work, the effects of total dose irradiation on the parasitic bipolar junction transistor (BTJ) in 130 nm PDSOI MOSFETs were investigated. The experimental results demonstrate that irradiation-induced oxide-trap charges can modify the E-B junction barrier, and thereby make the common-emitter gain β0 of the parasitic BJT in NMOS device increase, while decreasing it in a PMOS device. Additionally, irradiation-generated oxide-trap charges in shallow trench isolation (STI) elevate the surface electrostatic potential of the gate above the STI sidewall, thus providing an additional channel from the emitter to the collector. Moreover, these charges may generate parasitic reverse conductive paths at the STI/Si interface under high dose irradiation, thereby enhancing the leakage current in the front gate channel and diminishing the significance of the parasitic BJT. Under irradiation, the electric field intensity difference between two biases leads to higher β0 of the parasitic BJT in PG-biased devices than in ON-biased ones. Furthermore, the lifting effect of irradiation on β0 increases in wide or short channel irradiated devices, which can be explained using simulations and an emitter current crowding effect model. Full article
(This article belongs to the Section A:Physics)
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12 pages, 1748 KiB  
Article
Twenty Years of Advancements in a Radiotherapy Facility: Clinical Protocols, Technology, and Management
by Stefano Tomatis, Pietro Mancosu, Giacomo Reggiori, Francesca Lobefalo, Pasqualina Gallo, Nicola Lambri, Lucia Paganini, Francesco La Fauci, Andrea Bresolin, Sara Parabicoli, Marco Pelizzoli, Pierina Navarria, Ciro Franzese, Domenico Lenoci and Marta Scorsetti
Curr. Oncol. 2023, 30(7), 7031-7042; https://doi.org/10.3390/curroncol30070510 - 22 Jul 2023
Cited by 1 | Viewed by 2278
Abstract
Background: Hypo-fractionation can be an effective strategy to lower costs and save time, increasing patient access to advanced radiation therapy. To demonstrate this potential in practice within the context of temporal evolution, a twenty-year analysis of a representative radiation therapy facility from 2003 [...] Read more.
Background: Hypo-fractionation can be an effective strategy to lower costs and save time, increasing patient access to advanced radiation therapy. To demonstrate this potential in practice within the context of temporal evolution, a twenty-year analysis of a representative radiation therapy facility from 2003 to 2022 was conducted. This analysis utilized comprehensive data to quantitatively evaluate the connections between advanced clinical protocols and technological improvements. The findings provide valuable insights to the management team, helping them ensure the delivery of high-quality treatments in a sustainable manner. Methods: Several parameters related to treatment technique, patient positioning, dose prescription, fractionation, equipment technology content, machine workload and throughput, therapy times and patients access counts were extracted from departmental database and analyzed on a yearly basis by means of linear regression. Results: Patients increased by 121 ± 6 new per year (NPY). Since 2010, the incidence of hypo-fractionation protocols grew thanks to increasing Linac technology. In seven years, both the average number of fractions and daily machine workload decreased by −0.84 ± 0.12 fractions/year and −1.61 ± 0.35 patients/year, respectively. The implementation of advanced dose delivery techniques, image guidance and high dose rate beams for high fraction doses, currently systematically used, has increased the complexity and reduced daily treatment throughput since 2010 from 40 to 32 patients per 8 h work shift (WS8). Thanks to hypo-fractionation, such an efficiency drop did not affect NPY, estimating 693 ± 28 NPY/WS8, regardless of the evaluation time. Each newly installed machine was shown to add 540 NPY, while absorbing 0.78 ± 0.04 WS8. The COVID-19 pandemic brought an overall reduction of 3.7% of patients and a reduction of 0.8 fractions/patient, to mitigate patient crowding in the department. Conclusions: The evolution of therapy protocols towards hypo-fractionation was supported by the use of proper technology. The characteristics of this process were quantified considering time progression and organizational aspects. This strategy optimized resources while enabling broader access to advanced radiation therapy. To truly value the benefit of hypo-fractionation, a reimbursement policy should focus on the patient rather than individual treatment fractionation. Full article
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20 pages, 353 KiB  
Article
A Bi-Level Vaccination Points Location Problem That Aims at Social Distancing and Equity for the Inhabitants
by Edith Salinas, José-Fernando Camacho-Vallejo and Samuel Nucamendi-Guillén
Axioms 2023, 12(3), 305; https://doi.org/10.3390/axioms12030305 - 17 Mar 2023
Cited by 2 | Viewed by 2003
Abstract
Designing efficient vaccination programs that consider the needs of the population is very relevant to prevent reoccurrence of the COVID-19 pandemic. The government needs to provide vaccination points to give out vaccine doses to the population. In this paper, the authors analyze the [...] Read more.
Designing efficient vaccination programs that consider the needs of the population is very relevant to prevent reoccurrence of the COVID-19 pandemic. The government needs to provide vaccination points to give out vaccine doses to the population. In this paper, the authors analyze the location of vaccination points whilst addressing the inhabitants’ preferences. Two objectives that prevent crowding of inhabitants are considered. The government aims for the minimum distance between located vaccination points is maximized, and for the number of inhabitants that attend the different vaccination points to be equitable. One of the key aspects of this problem is the assumption that inhabitants freely choose the located vaccination point to go. That decision affects the objectives of the government, since crowding at vaccination points may appear due to the inhabitants’ decisions. This problem is modeled as a bi-objective, bi-level program, in which the upper level is associated to the government and the lower level to the inhabitants. To approximate the Pareto front of this problem, a cross-entropy metaheuristic is proposed. The algorithm incorporates criteria to handle two objective functions in a simultaneous manner, and optimally solve the lower-level problem for each government decision. The proposed algorithm is tested over an adapted set of benchmark instances and pertinent analysis of the results is included. An important managerial insight is that locating far vaccination points does not lead us to a more equitable allocation of inhabitants. Full article
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16 pages, 2805 KiB  
Article
Effects of Different Phospholipid Sources on Growth and Gill Health in Atlantic Salmon in Freshwater Pre-Transfer Phase
by Renate Kvingedal, Jannicke Vigen, Dominic Nanton, Kari Ruohonen and Kiranpreet Kaur
Animals 2023, 13(5), 835; https://doi.org/10.3390/ani13050835 - 24 Feb 2023
Cited by 2 | Viewed by 2544
Abstract
Growth and histological parameters were evaluated in Atlantic salmon (74 g) that were fed alternative phospholipid (PL) sources in freshwater (FW) up to 158 g and were transferred to a common seawater (SW) tank with crowding stress after being fed the same commercial [...] Read more.
Growth and histological parameters were evaluated in Atlantic salmon (74 g) that were fed alternative phospholipid (PL) sources in freshwater (FW) up to 158 g and were transferred to a common seawater (SW) tank with crowding stress after being fed the same commercial diet up to 787 g. There were six test diets in the FW phase: three diets with different doses of krill meal (4%, 8%, and 12%), a diet with soy lecithin, a diet with marine PL (from fishmeal), and a control diet. The fish were fed a common commercial feed in the SW phase. The 12% KM diet was compared against the 2.7% fluid soy lecithin and 4.2% marine PL diets, which were formulated to provide the same level of added 1.3% PL in the diet similar to base diets with 10% fishmeal in the FW period. A trend for increased weight gain with high variability was associated with an increased KM dose in the FW period but not during the whole trial, whereas the 2.7% soy lecithin diet tended to decrease growth during the whole trial. A trend for decreased hepatosomatic index (HSI) was associated with an increased KM dose during transfer but not during the whole trial. The soy lecithin and marine PL diets showed similar HSI in relation to the control diet during the whole trial. No major differences were observed in liver histology between the control, 12% KM, soy lecithin, and marine PL diets during transfer. However, a minor positive trend in gill health (lamella inflammation and hyperplasia histology scores) was associated with the 12% KM and control diets versus the soy lecithin and marine PL diets during transfer. Full article
(This article belongs to the Special Issue Nutritional Management to Promote Responsible Aquaculture)
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10 pages, 1601 KiB  
Article
A Principal Approach to the Detection of Radiation-Induced DNA Damage by Circular Dichroism Spectroscopy and Its Dosimetric Application
by Maria A. Kolyvanova, Mikhail A. Klimovich, Alexandr V. Belousov, Vladimir A. Kuzmin and Vladimir N. Morozov
Photonics 2022, 9(11), 787; https://doi.org/10.3390/photonics9110787 - 23 Oct 2022
Cited by 6 | Viewed by 2172
Abstract
Using cholesteric liquid-crystalline dispersion (CLCD) of DNA, we demonstrate that the molecularly organized systems may be used both for qualitative assessment of the degree of radiation-induced DNA damage, as well as for detection of radiation doses in a very wide range. The doses [...] Read more.
Using cholesteric liquid-crystalline dispersion (CLCD) of DNA, we demonstrate that the molecularly organized systems may be used both for qualitative assessment of the degree of radiation-induced DNA damage, as well as for detection of radiation doses in a very wide range. The doses up to 500 Gy do not cause any significant changes in optical signals of DNA in solution. However, when irradiated molecules are used to prepare the CLCD by addition of crowding polymer, a clear correlation of its optical signals with an absorbed dose is observed. For example, at a dose of 500 Gy, a maximum drop in the circular dichroism (CD) signal for DNA solution and for CLCD formed from preliminary irradiated molecules is ≈20% and ≈700%, respectively. This approach can also be used to expand the dosimetric capabilities of DNA CLCD. Compared to the case of irradiation of ready-made DNA CLCD, formation of the dispersed system from irradiated DNA allows to increase its sensitivity by more than 2 orders of magnitude. A similar decrease in the CD signal (≈1.45-fold) is observed in these systems at the doses of 100 kGy and 200 Gy, respectively. This principal approach seems to be relevant for other biomolecules and molecularly organized systems. Full article
(This article belongs to the Topic Liquid Crystal Photonics)
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27 pages, 678 KiB  
Systematic Review
Transmission of SARS-CoV-2 Associated with Cruise Ship Travel: A Systematic Review
by Elena Cecilia Rosca, Carl Heneghan, Elizabeth A. Spencer, Jon Brassey, Annette Plüddemann, Igho J. Onakpoya, David Evans, John M. Conly and Tom Jefferson
Trop. Med. Infect. Dis. 2022, 7(10), 290; https://doi.org/10.3390/tropicalmed7100290 - 9 Oct 2022
Cited by 12 | Viewed by 4729
Abstract
Background: Maritime and river travel may be associated with respiratory viral spread via infected passengers and/or crew and potentially through other transmission routes. The transmission models of SARS-CoV-2 associated with cruise ship travel are based on transmission dynamics of other respiratory viruses. We [...] Read more.
Background: Maritime and river travel may be associated with respiratory viral spread via infected passengers and/or crew and potentially through other transmission routes. The transmission models of SARS-CoV-2 associated with cruise ship travel are based on transmission dynamics of other respiratory viruses. We aimed to provide a summary and evaluation of relevant data on SARS-CoV-2 transmission aboard cruise ships, report policy implications, and highlight research gaps. Methods: We searched four electronic databases (up to 26 May 2022) and included studies on SARS-CoV-2 transmission aboard cruise ships. The quality of the studies was assessed based on five criteria, and relevant findings were reported. Results: We included 23 papers on onboard SARS-CoV-2 transmission (with 15 reports on different aspects of the outbreak on Diamond Princess and nine reports on other international cruises), 2 environmental studies, and 1 systematic review. Three articles presented data on both international cruises and the Diamond Princess. The quality of evidence from most studies was low to very low. Index case definitions were heterogeneous. The proportion of traced contacts ranged from 0.19 to 100%. Studies that followed up >80% of passengers and crew reported attack rates (AR) up to 59%. The presence of a distinct dose–response relationship was demonstrated by findings of increased ARs in multi-person cabins. Two studies performed viral cultures with eight positive results. Genomic sequencing and phylogenetic analyses were performed in individuals from three cruises. Two environmental studies reported PCR-positive samples (cycle threshold range 26.21–39.00). In one study, no infectious virus was isolated from any of the 76 environmental samples. Conclusion: Our review suggests that crowding and multiple persons per cabin were associated with an increased risk of transmission on cruise ships. Variations in design, methodology, and case ascertainment limit comparisons across studies and quantification of transmission risk. Standardized guidelines for conducting and reporting studies on cruise ships of acute respiratory infection transmission should be developed. Full article
(This article belongs to the Section Infectious Diseases)
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29 pages, 7665 KiB  
Article
In Silico Investigations of Multi-Drug Adaptive Therapy Protocols
by Daniel S. Thomas, Luis H. Cisneros, Alexander R. A. Anderson and Carlo C. Maley
Cancers 2022, 14(11), 2699; https://doi.org/10.3390/cancers14112699 - 30 May 2022
Cited by 8 | Viewed by 3440
Abstract
The standard of care for cancer patients aims to eradicate the tumor by killing the maximum number of cancer cells using the maximum tolerated dose (MTD) of a drug. MTD causes significant toxicity and selects for resistant cells, eventually making the tumor refractory [...] Read more.
The standard of care for cancer patients aims to eradicate the tumor by killing the maximum number of cancer cells using the maximum tolerated dose (MTD) of a drug. MTD causes significant toxicity and selects for resistant cells, eventually making the tumor refractory to treatment. Adaptive therapy aims to maximize time to progression (TTP), by maintaining sensitive cells to compete with resistant cells. We explored both dose modulation (DM) protocols and fixed dose (FD) interspersed with drug holiday protocols. In contrast to previous single drug protocols, we explored the determinants of success of two-drug adaptive therapy protocols, using an agent-based model. In almost all cases, DM protocols (but not FD protocols) increased TTP relative to MTD. DM protocols worked well when there was more competition, with a higher cost of resistance, greater cell turnover, and when crowded proliferating cells could replace their neighbors. The amount that the drug dose was changed, mattered less. The more sensitive the protocol was to tumor burden changes, the better. In general, protocols that used as little drug as possible, worked best. Preclinical experiments should test these predictions, especially dose modulation protocols, with the goal of generating successful clinical trials for greater cancer control. Full article
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14 pages, 2460 KiB  
Article
Protective Immunity Induced by an Eimeria tenella Whole Sporozoite Vaccine Elicits Specific B-Cell Antigens
by Marco A. Juárez-Estrada, Amanda Gayosso-Vázquez, Guillermo Tellez-Isaias and Rogelio A. Alonso-Morales
Animals 2021, 11(5), 1344; https://doi.org/10.3390/ani11051344 - 9 May 2021
Cited by 7 | Viewed by 4324
Abstract
This study investigated protection against Eimeria tenella following the vaccination of chicks with 5.3 × 106 E. tenella whole-sporozoites emulsified in the nanoparticle adjuvant IMS 1313 N VG Montanide™ (EtSz-IMS1313). One-day-old specific pathogen-free (SPF) chicks were subcutaneously injected in the neck with [...] Read more.
This study investigated protection against Eimeria tenella following the vaccination of chicks with 5.3 × 106 E. tenella whole-sporozoites emulsified in the nanoparticle adjuvant IMS 1313 N VG Montanide™ (EtSz-IMS1313). One-day-old specific pathogen-free (SPF) chicks were subcutaneously injected in the neck with EtSz-IMS1313 on the 1st and 10th days of age. Acquired immunity was assayed through a challenge with 3 × 104 homologous sporulated oocysts at 21 days of age. The anticoccidial index (ACI) calculated for every group showed the effectiveness of EtSz-IMS1313 as a vaccine with an ACI of 186; the mock-injected control showed an ACI of 18 and the unimmunized, challenged control showed an ACI of −28. In a comparison assay, antibodies from rabbits and SPF birds immunized with EtSz-IMS1313 recognized almost the same polypeptides in the blotting of E. tenella sporozoites and merozoites. However, rabbit antisera showed the clearest recognition pattern. Polypeptides of 120, 105, 94, 70, 38, and 19 kDa from both E. tenella life cycle stages were the most strongly recognized by both animal species. The E. tenella zoite-specific IgG antibodies from the rabbits demonstrated the feasibility for successful B cell antigen identification. Full article
(This article belongs to the Special Issue Alternative Methods for Control of Pathogens in Livestock)
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11 pages, 907 KiB  
Article
Investigation of Measles Outbreak among Thai and Migrant Workers in Two Factories in Nakhon Pathom, Thailand, 2019
by Suphanat Wongsanuphat, Phanthanee Thitichai, Rungrot Jaiyong, Patchanee Plernprom, Kanthika Thintip, Charuttaporn Jitpeera and Rapeepong Suphanchaimat
Int. J. Environ. Res. Public Health 2020, 17(13), 4627; https://doi.org/10.3390/ijerph17134627 - 27 Jun 2020
Cited by 7 | Viewed by 3363
Abstract
On 22 March 2019 the Thai Department of Disease Control (DDC) was notified that 16 workers, including Thai and Myanmar migrant workers, from two factories located in Nakhon Phathom Province, had presented with a fever with rash during the previous 2 weeks. Active [...] Read more.
On 22 March 2019 the Thai Department of Disease Control (DDC) was notified that 16 workers, including Thai and Myanmar migrant workers, from two factories located in Nakhon Phathom Province, had presented with a fever with rash during the previous 2 weeks. Active case finding was conducted among workers in both factories using face-to-face interviews. Suspected cases were defined as a worker who developed fever with rash with one of the following symptoms: cough, coryza or conjunctivitis. Testing for measles IgM antibodies and viral identification through throat swabs by polymerase chain reaction (PCR) were performed to confirm diagnosis. Vaccination history among cases was reviewed. Nationality and age-specific attack rates (AR) were calculated. An environmental study and a social network analysis were conducted to better understand the transmission process. A total 56 cases (AR = 0.97%) were identified. Of 21 serum measles IgM collected, 8 (38.0%) were positive. Of 8 throat swabs collected, 5 (62.5%) were positive for measles genotype D8. The disease attack rate in migrant employees was twice as large as the rate in Thai counterparts (AR = 0.7 and 1.4%). The first case was identified as a Myanmar worker who arrived in Thailand two weeks prior to his illness. The Myanmar workers’ accommodation was more crowded than that for Thai workers. The hot spots of transmission were found at a drinking water tank which had shared glasses. Among the cases, 62.5% could not recall their vaccination history, and 25% had never had an injection containing a measles vaccination. The majority of migrant cases had never completed a two-dose measles vaccination. To halt the outbreak, measles vaccines were administered to the employees, particularly those working in the same sections with the cases and shared glasses were removed. For future policy action, a vaccination program should be incorporated into the work permit issuance process. Full article
(This article belongs to the Special Issue Health and Health Care Access of Vulnerable Populations)
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14 pages, 46513 KiB  
Article
Tracing Actin Filament Bundles in Three-Dimensional Electron Tomography Density Maps of Hair Cell Stereocilia
by Salim Sazzed, Junha Song, Julio A. Kovacs, Willy Wriggers, Manfred Auer and Jing He
Molecules 2018, 23(4), 882; https://doi.org/10.3390/molecules23040882 - 11 Apr 2018
Cited by 14 | Viewed by 6364
Abstract
Cryo-electron tomography (cryo-ET) is a powerful method of visualizing the three-dimensional organization of supramolecular complexes, such as the cytoskeleton, in their native cell and tissue contexts. Due to its minimal electron dose and reconstruction artifacts arising from the missing wedge during data collection, [...] Read more.
Cryo-electron tomography (cryo-ET) is a powerful method of visualizing the three-dimensional organization of supramolecular complexes, such as the cytoskeleton, in their native cell and tissue contexts. Due to its minimal electron dose and reconstruction artifacts arising from the missing wedge during data collection, cryo-ET typically results in noisy density maps that display anisotropic XY versus Z resolution. Molecular crowding further exacerbates the challenge of automatically detecting supramolecular complexes, such as the actin bundle in hair cell stereocilia. Stereocilia are pivotal to the mechanoelectrical transduction process in inner ear sensory epithelial hair cells. Given the complexity and dense arrangement of actin bundles, traditional approaches to filament detection and tracing have failed in these cases. In this study, we introduce BundleTrac, an effective method to trace hundreds of filaments in a bundle. A comparison between BundleTrac and manually tracing the actin filaments in a stereocilium showed that BundleTrac accurately built 326 of 330 filaments (98.8%), with an overall cross-distance of 1.3 voxels for the 330 filaments. BundleTrac is an effective semi-automatic modeling approach in which a seed point is provided for each filament and the rest of the filament is computationally identified. We also demonstrate the potential of a denoising method that uses a polynomial regression to address the resolution and high-noise anisotropic environment of the density map. Full article
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