The industrial polymeric carriers for peroral mesalazine application exploit, i.a., cellulose or polyacrylic acid derivatives, polyvinylpyrrolidone, and modified starch. Pectins, as natural polymers, are interesting materials in pharmaceutical applications due to properties such as non-toxicity, biocompatibility, and biodegradability. The aim of the study was the evaluation of the release of the drug from coated pectin beads doped with synthetic polymers as drug carriers to the colon, as well as interactions between ingredients. The drug release was carried out using basket apparatus. The amount of 5-ASA  released to the pH = 7.4 buffer with pectinase was measured at selected time intervals using UV-Vis spectroscopy. The zero-, first-, and second-order kinetics, as well as Higuchi, Korsmeyer–Peppas, and Hixon–Crowell equations, were used to analyze the release pattern. The interactions between beads components were investigated employing FTIR spectrophotometry and DSC study. The dissolution of the drug was divided into two parts. It was found that the release of 5-ASA followed mainly the Higuchi equation. The mass transport in the first stage of the release followed a non-Fickian model and the parameter n was in the range of 0.74 ± 0.2–0.99 ± 0.2. The formulation doped with PA (polyacrylic acid) was the most appropriate and capable of overcoming the variable conditions of the gastrointestinal tract. Pectin is a natural polysaccharide occurring in the walls of plants . The amoA modified form of pectin is amidated pectin. Its chain contains some of the galacturonic acid molecules changed using ammonia to a carboxylic acid amide. The in vitro and in vivo study showed that pectins and amidated pectins were degraded in the upper parts of the digestive tract, although they were fermented by intestinal microbiota during their passage through the large intestine in animals and humans . In planPectin shows biocompatibility and biodegradability and therefore was used in medicine and pharmacy. It has antimicrobial and antiviral properties, decreases water solubility, and improves mechanical properties. It is a very good biomaterial for drug carriers, antimicrobial films, and coatings. It is also a good material for hydrogels, films, scaffolds, and nanoparticles formations . It was Slavutsky et al.  revealedThe aim of the study was to obtain coated pectin beads doped with various synthetic polymers for colon targeted drug delivery systems and evaluate the kinetics of the drug-mesalazine (5-ASA) release from the formed carriers. The cores of coated beads consisted of a natural polymer–pectin and a doped synthetic polymer and were named bipolymeric milibeads. Additionally, the interaction between polymers and the drug with polymers was carried out.Amidated pectin (APN) was supplied from C&G . Calcium chloride and tris(hydroxymethyl)aminomethane were obtained from Chempur . Hydrochloric acid was bought in StanLab . Polyacrylic acid (PA) was delivered from Lubrizol  and ammonium acryloyldimethyltaurate (AX) from CLARIANT . Polyethylene glycol (PEG) 4000 was a gift from the local industry Hasco-Lek . Thirty percent dispersion of polyvinyl acetate stabilized with polyvinylpyrrolidone and sodium lauryl sulfate (PVAC-D) was supplied from BASF . A blend of polyvinyl acetate and povidone in the ratio 8:2 (PVAC-P) was supplied from BASF . The 5-aminosalicylic acid (5-ASA) was obtained from Sigma–Aldrich  and pectinase was bought in BROWIN . All reagents were of analytical grade and were applied without additional purification.w/v) in formulations F1–F5 and APN 4.3% (w/v) in formulations F1 and F6. In formulations F2–F5 and F7–F10, the amount of APN was 3.6% (w/v), and the synthetic polymer was approximately 0.7% (w/v). The solution was instilled through a needle (20 G) into a 2.0% solution of calcium chloride employing the peristaltic pump  with a flow speed of 2.0 mL/min. Calcium chloride solution was placed on the magnetic stirrer  with a rotation speed of 200 rpm. The obtained pectin beads were removed from the solution, washed with water, and dried at the temperature of 50 °C until the difference in mass between the measurements performed within 30 min was less than 0.5 mg [v/v). The obtained dispersion was sprayed on the beads. The beads were dried and mixed at the temperature of 50 °C for about 4 h. The spraying and drying procedure was repeated three times. Finally, the mass of coated beads was determined. The coating mass deposited on the milibeads was calculated as a difference between uncoated and coated milibeads.The pectin beads were obtained by applying the ionotropic gelation method . Accordin 0.5 mg . The driThe microscopic investigation was carried out employing a microscope  coupled with a Moticam camera. The surface area of about 60 beads of each formulation was measured using the dedicated software Motic Plus 2.0 . The microscope magnification was fixed to 7.5. The microscopic images of 60 weighted beads were recorded. The program calculated the area of each bead separately, and the mean value was calculated. The mean surface area per mean mass of all formulations, as well as the standard deviation (SD), were calculated, applying the above-presented procedure.tav/m0av, where mtav was the average mass of the sample at selected time point t and the m0av was the average mass of the sample at the beginning of the study. The standard deviation (SD) was calculated as well.The stability of the carriers of F6–F10 was investigated in buffer solutions with pH = 1.0; 6.0 and 7.4 with pectinase. The sample of the dry formulation was weighed, placed in a sieve, and immersed in a pH = 1.0 buffer for 2 h. The beads were removed from the solution, dried with a paper towel at defined time intervals, and the mass was measured using an analytical balance . After 2 h of the test, the beads were removed from pH = 1.0 buffer and placed in pH = 6.0 buffer for the next 2 h, and the weighing procedure was repeated. Finally, after 4 h from the beginning of the test, the beads were placed in pH = 7.4 buffer with pectinase and weight every 15 min in the same way as previously. Each formulation F6–F10 was studied twice to calculate the value of mt is the amount of the drug released in time t; mb is the amount of the drug in the solution before the release ; m0 is the amount of the drug in the formulation before the dissolution; m∞ is the amount of the drug released after the infinitive time (in this research after 8 h); mleft is the amount of the drug left in the formulation in time t; k0, k1, k2, kH; kK−P, kH−C mean the zero-, first-, second-order, Higuchi, Korsmeyer–Peppas and Hixon–Crowell release rate constants, respectively; n is the parameter indicative of the drug release mechanism. The comparison between the release profiles was carried out based on the values of the difference factor f1 and the similarity factor f2 (Equations (7) and (8)):t is the released value of the reference batch at time t, and Tt is the released value of the test batch at time t [The release of 5-ASA from formulations F1–F5 was carried out employing the dissolution apparatus 1  . The temt time t .p-value of 0.05 was taken as the minimum level of significance. The comparison between the dissolution curves was also conducted employing ANOVA and Tukey’s HSD test on a 95% confidence level [The obtained results of the surface area per mass of beads were shown as the means and ± SD. The statistical properties of the surface area per mass of coated pectin beads F1–F10 were performed based on the one-way analysis of variance (ANOVA) method and Honestly Significant Difference test (Tukey’s HSD), and a ce level .−1. The spectra were an average of 32 scans at a resolution of 4 cm−1. The recorded data were analyzed using a dedicated computer program OMNIC Specta 2.0 .FTIR spectra of F1–F10 beads, as well as the corresponding physical mixtures, were recorded using FTIR spectrometer  coupled to ATR mode  in the wavelength range of 500–4000 cmThe images of the obtained coated formulations F1–F5 loaded with 5-ASA were shown in 2/g and was higher than the surface area per mass of formulations F6–F10 unloaded with 5-ASA, which was in the range from 2.2 ± 1.1 to 3.7 ± 2.6 mm2/g. The incorporation of synthetic polymers such as PA, PEG, AX, PVAC-P to the beads loaded with 5-ASA affected the value of the surface area per mass. The value of the surface area per mass of F2, F3, F4, F5 was higher than the value obtained for the F1 formulation (3.8 ± 1.0 mm2/g) not containing the synthetic polymer. Moreover, the incorporation of PA to unloaded with 5-ASA beads (F7) increased the surface area per mass in comparison to the value obtained for F6 not doped with the synthetic polymer. Additionally, the discrepancies between the surface area per mass of beads containing different synthetic polymers were revealed. The surface area per mass of F3 with PEG was 8.2 ± 4.2 mm2/g, and it was higher than the surface area per mass of F4 and F5 containing PA, AX, and PVAC-P. The values obtained for F2, F4, and F5 were similar, and they were in the range from 5.8 ± 1.2 to 6.0 ± 3.6 mm2/g. However, in the case of unloaded beads, the surface area per mass of F7 doped with PA was the highest among formulations F7–F10. The results of the surface area per mass of the beads study indicated that the addition of the second polymer PA, AX, or PVAC-P to the loaded with 5-ASA beads provoked the formation of more compact beads than the formulation doped with PEG. In the case of beads unloaded with the drug, the most compressed formulations were doped with PEG, AX, and PVAC-P as well as formulation without the synthetic polymer. A similar observation was found in Calvo et al.’s studies [The average surface area per mass of all formulations was analyzed, and the results were presented in  studies . It may  studies ,21.The incorporation of synthetic polymers, as well as 5-ASA to the coated pectin preparations, influenced the value of the surface area per mass of the beads studied.The carrier stability investigation was performed at pH = 1.0, simulating the stomach environment, pH = 6.0 that reflect intestines conditions, as well as at pH = 7.4 with pectinase reflecting the colon environment. The obtained results were presented in Based on these results, it can be concluded that the most promising formulation was F7 doped with PA. It is consistent with the observation from the morphological study. The incorporation of PA to F2 gave more compact beads that were more stable and could overcome the variable conditions of the digestive tract.a1 (carboxyl) = 2.30 ± 0.09 and pKa2 (amino) = 5.69 ± 0.04 [The dissolution curves of the drug released to the pH = 1.0 solution were presented in 9 ± 0.04 . Aunis e9 ± 0.04 , in thei9 ± 0.04 , the druThe maximum percent of the drug released to the pH = 7.4 buffer with pectinase was 71.0 ± 2.0% and was obtained from beads F5. Next to this was observed for the release of the drug from F4, and it was 69.0 ± 7.0%. The percent of the drug released from the F1 formulation was 67.0 ± 2.0% and from F3 was 65.0 ± 4.0%. The lowest amount of the drug released was 44.0 ± 12.0%, observed in the case of the dissolution of 5-ASA from F2 formulation. It was consistent with results obtained from the carrier stability study. The most stable beads in the colon environment were beads F2 doped with PA.Based on the results presented in The estimated pH of F2 beads was about 3.0 that favors the low solubility of 5-ASA. The increasing pH in the buffer solution to 7.4 causes an increase in the drug concentration in the acceptor medium . AdditioThe drug release patterns of formulations F1–F5 to the pH = 7.4 buffer with pectinase were presented in 2) obtained for the first release stage were in the range from 0.83 ± 0.04 to 0.99 ± 0.01. However, the first stage of the drug release from F1–F3 was best described by the Higuchi model. In the case of 5-ASA release from F4 and F5, the second-order kinetics was more suitable. According to the Higuchi model, the drug was released the fastest from F3 with the rate constant 43.1 ± 3.6 mg × min−1/2 and a half release time of 40.06 ± 6.6 min. The lowest value of kH and the highest of t0.5 were obtained for the release of the drug from F4. However, based on the results from the second-order equation, the lowest value of the rate constant kS-O = (1.5 ± 0.2) × 10−5 mg−1 × min−1 and the highest value of t0.5 = 187.3 ± 39.1 min were calculated for the dissolution of 5-ASA from F2. Additionally, the lowest value of the rate constant and the highest value of the half release time was obtained in the case of the drug release from F2 also using Z-O, F-O, H–C models.The kinetic release parameters were determined for both stages of the dissolution and were listed in It is consistent with the results presented in t/m∞ < 0.6 may be used. In the present investigation, this portion was included in the first stage of the dissolution curve, and neither n value nor the other kinetic parameters on the basis of the K–P model for the second stage release study were determined. The kinetic parameters obtained for the second stage of the dissolution employing other kinetic models were presented in Costa et al.  and Suva−1/2, and the half release time was 234 ± 83 min. The lowest value of kH = 1.9 ± 0.2 mg × min−1/2 was obtained for the drug dissolution from F5, and t0.5 was 9304 ± 2776 min. Similar results were found in the case of the Z-O model. However, from S-O kinetics, the highest value of k2 was derived for 5-ASA release from F2, similar to the first stage and the lowest for the drug release from F4 beads. Analysing the obtained rate constants, it was noticed that in Z-O, F-O, H, H–C models, 5-ASA was released the slowest from F5, in contrast to the first step where the drug release rate constants from F5 were the highest in most cases. It should be mention that the variability between the kinetic parameters was not significant; values were of the same order of magnitude.The values of linear correlation coefficients calculated for the second stage of the release were in the range from 0.80 ± 0.01 to 0.91 ± 0.05 and were slightly lower than in the first stage of the dissolution. The best fit was obtained using the Higuchi model describing the drug release from all formulations studied apart from F3. Based on this model, the drug was released the fastest from F2 with the release rate constants of 5.2 ± 0.8 mg × minThe main idea of the work was to study the release kinetics of the drug at pH = 7.4 in the presence of an enzyme, which reflected the colon environment. The stability investigations were performed in three different media, which reflected the pH of the consequent parts of the digestive tract environment. The study revealed that the beads might overcome the variable pH conditions of the gastrointestinal tract and may reach the large intestine. The dissolution plots in low pH were obtained additionally to gain more information on the drug release during beads swelling.1 are close to 0, usually are in the range 0–15. The values of f2 close to 100, usually from the range from 50–100, indicate sameness or equivalence of the compared profiles [1 and f2 were summarised in 1 and f2 did not indicate discrepancies. It should be noticed that the differences were also observed between the release profiles of F2 and F3, F4, F5. It can be concluded that the analysis of f1 and f2 parameters indicated the difference between the release of 5-ASA from F2 doped with PA and from the rest formulations. The incorporation of PA to the beads changed the release behavior.In order to compare the release curves of 5-ASA from formulations F1–F5, the difference factor and the similarity factor were calculated. FDA recommended that the dissolution profiles are similar if the values of fprofiles . In the 1 and f2 calculations.The release profiles of 5-ASA from formulations F1–F5 were analyzed employing ANOVA. It was found that there were statistically significant differences between groups. According to Tukey’s HSD test, the calculated value of HSD was 11.6, and the obtained values of differences between group means were listed in −1 that may be connected with the presence of the water molecule. The other maxima were recorded at 2918 and 2850 cm−1, the characteristic stretching vibration belonging to the C=O group was noticed at 1707 cm−1, and the band located at 1243 cm−1 was assigned to the C–O group. Additionally, the signals at 1654, 1421, 1375, 1087, and 835 cm−1 were also noticed, and the observations were in good agreement with the results obtained by D’Amelia et al. [−1 that was shifted to 1637 cm−1 in the spectra of F1–F10. Only in the case of the F5 spectrum, the band at 1637 cm−1 was not observed. In this region, the bands at 1650 and 1617 cm−1 belonging to 5-ASA were found. This observation may suggest the interaction between PVAC-D and APN that was present in all formulations F1–F10. Additionally, it was revealed that the maximum of APN at 1736 cm−1 present in all uncoated beads disappeared in the spectra of formulations of F1–F10 [The spectroscopic studies of pure ingredients of beads, uncoated formulations loaded and unloaded with the drug, as well as their corresponding physical mixtures, were carried out in our previous work . In the a et al.  and Wei a et al. . It was −1 may also be connected with the interaction between the coating and the synthetic polymers. The band of pure PA at 1697 cm−1 was not found in the spectra of uncoated beads nor in the spectra of coated beads, indicating the possibility of the interaction of PA with APN as well as with PVAC-D. This observation was consistent with the results obtained in the stability study (The new band observed at 1637 cmty study  and may The interaction between PA and PVAC-D may also explain the differences in the release of 5-ASA from F2 comparing the dissolution of the drug from F1. The statistical analysis indicated the discrepancies in the release of 5-ASA from F2 and from the rest formulations as well. Sahariah et al.  studied −1 was found only in the spectrum of the F3 physical mixture but was not present in the spectra of F3 nor in F8. The observation was consistent with the result of the uncoated beads study in which the interaction between the hydroxyl groups of PEG 4000 and APN was postulated. The band at 1096 cm−1 belonging to PEG 4000 was noticed only in the spectrum of the physical mixture of F3 but was shifted to1076 cm−1 in the spectra of F3 and F8. However, it was difficult to assign the signal unambiguously to PEG 4000 because, at 1087 cm−1, the characteristic maximum of PVAC-D was observed. The appearance of a new band at 1076 cm−1 cannot exclude the bond formation between PEG 4000 and PVAC-D. Wu et al. [In the case of formulation F3 doped with PEG 4000, the signal of the synthetic polymer at 2881 cmu et al.  revealed−1 were not noticed, similar to the study of uncoated beads. Besides the interaction of AX with APN, the carbonyl groups of the synthetic polymer may also bind to the coating carbonyl group, and it was difficult to distinguish which molecule interacts with AX. It was also possible that both of them form a bond. The analysis of the FTIR spectra of F5, its physical mixture, and F10 gave analogous results. The characteristic bands of PVAC-P at 1731 and 1661 cm−1 were found in the spectrum of the F5 physical mixture at 1731 and 1673 cm−1, but both disappeared in the spectra of F5 and F10 formulations. The beads were incorporated with PVAC-P, which carbonyl groups may interact with carbonyl groups of APN as well as PVAC-D.The FTIR spectra of F4, its physical mixture, and F9 were presented in −1 in the spectra of physical mixtures indicated the presence of CaCl2, and they disappeared in the spectra of formulations F1–F10 because a chemical bond of Ca2+ with APN was formed. The spectroscopic study confirms that the coating of the beads may increase the stability of the formulation by a bond formation and ensure to reach the large intestine.The maxima observed at the wavelength about 3489 and 3448 cmIn our previous paper, we evaluated the uncoated beads, whereas, in the present work, we presented the results obtained for coated formulations. The further study will evaluate the most promising beads-doped with PA–coated with another polymer to obtain a more effective cessation of the release of the drug in the stomach at low pH. On the other hand, the limited release of mesalazine in the gastric fluid may be beneficial in some cases. The last decade has brought more and more information about the changes in the stomach and duodenum accompanying ulcerative colitis. The use of a mesalazine preparation in which a part of the active ingredient is released in the stomach may favorably influence the course of treatment of complex inflammatory lesions within GT ,36,37,38The widely applied polymers used in the formulation of mesalazine are cellulose or polyacrylic acid derivatives, polyvinylpyrrolidone, and modified cellulose. In our research, the incorporation of synthetic polymers such as PA, PEG, AX, and PVAC-P into the beads loaded with 5-ASA resulted in an increase in the surface area per mass comparing to the surface area per mass of formulations not containing the synthetic polymer. However, the addition of the second polymer PA, AX, and PVAC-P to the beads loaded with 5-ASA provoked the formation of more compact beads in comparison to the formulation doped with PEG. The addition of PA to the beads, as well as the coating, prolonged the stability of the carrier in acidic conditions. The lowest amount of the drug released to the buffer of pH = 7.4 with pectinase was 44.0 ± 12.0% and was observed in the case of the dissolution of 5-ASA from F2 formulation doped with PA. The release process was divided into two stages. The drug release was well fitted to the Higuchi model and to the second-order kinetics. The obtained value of the parameter n from the K–P equation was in the range of 0.74 ± 0.2–0.99 ± 0.2, which indicates the non-Fickian model mass transfer. FTIR and DSC studies indicated the possibility of the bond formation between synthetic polymers and APN or coating polymers.The conducted research revealed that the F2 formulation, doped with PA and coated with a synthetic polymer, was the most promising formulation capable of overcoming the variable conditions of the gastrointestinal tract and delivering the drug to the colon.


Bemisia argentifolii , were also evaluated. The district is a dry tropical environment with a clear break to commercial production during the summer wet season. The incidence of TYLCV within crops and its prevalence through the district was influenced by weather, location, vector movements, and the use of Ty-1 virus-resistant hybrids. Rainfall had an important influence, with late summer and early autumn rain suppressing the levels of SLW and, by contrast, a dry summer supporting faster population growth. The use of Ty-1 hybrids appears to have reduced the incidence of TYLCV in this district. There was limited use of Ty-1 hybrids during 2013, and by season end, crops had moderate levels of SLW and high virus incidence. The 2015 and early 2016 season had high SLW populations, but TYLCV incidence was lower than in 2013, possibly due to the widespread adoption of the Ty-1 hybrids reducing virus spread. This study provides valuable epidemiology data for future incursions of begomoviruses, and other viruses spread by SLW.Early detection of tomato yellow leaf curl virus (TYLCV) in a previously unaffected tomato production district in Australia allowed its spread to be evaluated spatially and temporally. The population dynamics of the TYLCV vector,  Bemisia genus (Hemiptera: Alyerodidae) [Bemisia argentifolii  currently recognises 408 species within the Begomovirus genus . Begomovrodidae) . This in tabaci; ), biotypd by SLW ,6. Howevtomato yellow leaf curl virus–IL strain (TYLCV-IL) and tomato leaf curl virus (ToLCV), which largely only affect solanaceous crops [sweet potato leaf curl virus (SPLCV) which affects sweet potato crops, Abutilon mosaic virus (AbMV), and honeysuckle yellow vein mosaic virus (HYVMV) [Begomovirus diversity in Australia is extremely low, with only five known species. These are us crops . ToLCV hus crops . The rem (HYVMV) , and the (HYVMV) . Similar (HYVMV) . There a (HYVMV) .Globally, in regions with a high diversity of begomoviruses, particularly where the viruses have common hosts, recombination between different individual virus species can occur and give rise to a new virus species with an altered host range. This makes control and management of the diseases a constant challenge, particularly if control is dependent on host resistance. The threat to Australia posed by begomovirus incursions is substantial, and its possible viruliferous whiteflies could be blown into northern Australia from other countries. Timor Leste and Papua New Guinea are known to have begomoviruses exotic to Australia . The conhttps://www.abc.net.au/news/2010-07-06/seedling-sabotage-devastates-farmers/894442; accessed on 24 January 2022). As a direct consequence, late-season plantings of 2010 seedlings were unavailable locally, and a large volume was sourced from districts where TYLCV was common. Diagnostics samples sent from the district in early 2011 confirmed the presence of TYLCV-IL.TYLCV is highly destructive to tomato crops wherever it occurs . TYLCV-ITy-1 resistance gene, helps reduce economic losses from TYLCV, there are few other known resistance genes to other begomovirus species, thus it is unlikely that host resistance will be available if new begomoviruses are introduced into Australia. Consequently, it was important to understand how begomoviruses establish and spread to mitigate losses from potential future incursions. The early detection of TYLCV in a commercial production district allowed investigation of the establishment and spread of this virus in a newly affected area. Furthermore, unlike the southeast, the dry tropical environment has a clear break in cropping due to the annual wet season, and the district is limited in alternative weed and crop hosts of the virus over this break [Although host resistance, through the is break . These fThis paper describes the epidemiology of TYLCV in commercial tomato crops grown in a dry tropical environment over a four-year period soon after its introduction into the region. It also describes the environmental factors influencing whitefly populations, particularly rainfall.Potential change in virus diversity was monitored by whole genome sequencing of reference TYLCV isolates collected in the Bowen district in 2011, 2013, and 2015. There was very little diversity in the TYLCV genome from these sequenced isolates. Between the 2011 and later isolates, there was 99.6% similarity, and between 2013 and 2015, 99.8%. All three isolates were 98.5% identical to the initial 2006 Brisbane isolate of TYLCV-IL.Ty-1 resistance gene in 2015. There was a site influence on virus incidence in crop and SLW populations, with sites in area B often having more TYLCV than those in the A or C  compared to 34/59 sites (57.6%) after 2014. This difference was, however, not statistically significant in a one-way ANOVA test (results not shown).Monitoring vector populations for viruliferous adults revealed variation in relation to the percent of individuals carrying TYLCV. Of note is the variation between the incidence of TYLCV within a tomato crop and the percent of viruliferous SLW collected from that crop . Sites wTy-1. Large commercial trials of Ty-1 hybrids occurred in 2014, and the hybrids were almost uniformly adopted in 2015 and 2016, except for a few susceptible crops grown early in 2016. Before 2015, there were 13 examples of migratory SLW with higher viruliferous percentages than in crop virus incidence and only two examples after 2014. Conversely, there were 14 examples of migratory SLW populations with lower viruliferous percentages than virus incidence in crops after 2014, and only two examples before 2015  and then almost no further rainfall until the following January. SLW numbers during 2015 were high early, at least 4-fold higher than for the similar time point in 2013 and 2014. The population continued to build at a similar rate to 2013, about 3-fold by season end. The 2015–2016 summer wet season was unusually dry, with less than 50 mm of rainfall until January 2016. The 2016 summer rainfall was lower than previous years, and this, in combination with very high SLW numbers at the end of 2015, contributed to the high whitefly populations detected during May 2016. The high rainfall in June (>100 mm) and following rain in September led to the lower insect populations detected during the remainder of that season. The SLW population decreased by about 4-fold in 2016 by season end compared to 2013 and 2015, which were dry through the season and had increasing SLW populations. No obvious trends at the site within the districts  among the population levels of SLW were detected.Evaluation of weather data indicated the amounts and timing of rainfall influences populations of SLW, with wet autumn weather decreasing populations compared to drier conditions. No obvious differences were observed for average minimum or maximum temperatures across the four years of study. During the study, the highest SLW numbers were recorded in late 2015 and early-2016 . The 201The relatively recent introduction of TYLCV into a new production district allowed the spread of a begomovirus to be monitored spatially and temporally in a dry tropics environment which has a clear break in crop production. This provided insight into how quickly the virus established and spread within this environment and how weather influences vector and virus distributions.Ty-1 virus-resistant hybrids. Vector populations were influenced by the intensity and timing of rainfall and not by location. Dry conditions favoured SLW population increases compared to wet conditions, which do the opposite. There was very limited use of Ty-1 hybrids pre-2013 or during the 2013 season, and by season end, crops had moderate levels of SLW and high virus incidence. The 2014 season had some Ty-1 crops and was highly influenced by rainfall which kept SLW numbers at low levels all season, and consequently, TYLCV incidences were also low to moderate. Conversely, the 2015 season and start to the 2016 season had high SLW populations, driven by an unusually dry summer. Most crops in the 2015 and 2016 seasons used Ty-1 hybrids. The exception was a few crops in early 2016. Although SLW levels were higher during these seasons than observed in 2013, TYLCV incidence was lower, probably due to the widespread adoption of the Ty-1 hybrids lowering virus spread.The incidence of TYLCV within crops and its prevalence throughout the production district was shown to be influenced by vector populations, crop location, and the use of in planta in resistant hybrids and changes in SLW feeding preferences based on virus infection. This supports the observed field results from the current study. There was a reduction in the incidence of TYLCV within crops since the widespread adoption of resistant hybrids across the dry tropics district; however, although the incidence was reduced, virus spread continued. The distribution of TYLCV across the district was not overly influenced by using resistant hybrids as the virus was detected at all sites by season end in 2016. There were also fewer detections of migratory viruliferous SLW populations detected after adopting the resistant hybrids. This is partly explained by the lower transmission efficiency from Ty-1 crops during the season. Once primary spread from weeds has occurred early in the season, the major reservoirs of virus for continued spread during the season are the tomato crops, as multiple sequential plantings are done throughout the season. Where these crops are a resistant hybrid, virus transmission is less efficient, thus reducing the likelihood of detection of migratory viruliferous SLW populations.Lapidot et al. ,23 reporTy-1 resistant compared to susceptible hybrids. This did not, however, translate to differences in transmission efficiencies in controlled experiments [Ty-1 hybrids will result in a reduction of TYLCV in susceptible hybrids because the resistant ones are a reservoir for the virus and can support SLW populations. The results from the current study indicate this is not the case. It is reasonable to expect that the lowered acquisition efficiencies will impact field transmission due to a high likelihood of SLW populations having a lower proportion of viruliferous adults. Our results show for seasons where Ty-1 crops were predominantly grown (2015 and 2016), the average percentage of viruliferous SLW was vastly less than detected during seasons of susceptible crops (2013–2014). Our results have also shown lower TYLCV incidences occurred within the district despite high SLW pressure for seasons where Ty-1 hybrids are mostly grown. Although data on virus incidence in susceptible hybrids is limited, in early 2016, almost half of the survey sites had a susceptible hybrid, and there was either a low incidence of TYLCV or no virus detected from these crops. This was with the highest SLW pressure recorded during the study.Legarrea et al.  reportederiments . Srinivaeriments  suggest Trianthema portulacastrum, Solanum americanum, and Amaranthus viridis in the Bowen production district. Of these, S. americanum is a preferred host of SLW in this district, whereas the other two species are not. S. americanum, however, is mostly low in abundance during the summer wet season, as is A. viridis, whereas T. portulacastrum has a high abundance [The abundance of alternative hosts for TYLCV during the non-cropping season is also important in understanding virus disease outbreaks. Campbell et al.  reportedbundance . The majbundance . There iTy-1 hybrids allow profitability to continue in the presence of TYLCV, the introduction of another tomato-infecting begomovirus into Australian production districts would result in major economic losses. It would be unlikely that host resistance would be a viable solution, even if available, as it would be difficult to introgress more genes into a background already requiring resistance to five other pathogens. For other tropical and subtropical Australian vegetable crops, the outcome would be similar due to the low availability of virus resistance genes. Instead, monitoring seasonal weather patterns and strategic deployment of insecticides, biological control agents, and weed control would be essential to allow profitable production to continue.Understanding the impact of a newly introduced begomovirus requires information on virus and vector host ranges, the likely access to host-virus resistance, and the seasonal weather patterns which strongly affect whitefly population dynamics. Although the This study has shown that a begomovirus within a dry tropical environment can easily establish within a single growing season and spread to all areas of susceptible hosts within the district within two growing seasons. It provides very little time for industry to respond to a new disease threat. Further preparedness research is needed to develop strategies to manage begomoviruses. Research is also needed to evaluate other tropical and sub-tropical production districts within Australia to better predict impacts from newly introduced begomoviruses.Potential change in virus diversity was monitored by whole genome sequencing of reference TYLCV isolates collected in the Bowen district in 2011, 2013, and 2015. Full genome sequences were created by Sanger sequencing overlapping PCRs created using the primer pairs: TY_214_F (5′-TACGAGCCCAATACATT GGGC-3′) and TY_1339_R (5′-GATAAGATTCAACCACAACATCAG-3′), TY1019_F (5′-GCCTCTAATCCAGTGTATGCAACTATG-3′) and TY_2016_R (5′-GAACGTCGT ATCTTCCGCTGCGCGG3′), TY_1759_F (5′-CCGTACTTTGTGTTGCTTTGCCAGTCC-3′) and TY_394_R (5′-GCTGCTGTATGGGCTGTCGAAGTTC-3′).Surveys of tomato crops were completed from 2013 to 2016. This was done at three-time points, approximately two months apart, during the commercial production period (March to November). Survey sites were spread across the three major production areas within the district, which are approximately 5–20 km from each other .Survey sites were selected along the edges of crop production blocks, particularly corners where possible, as these are closest to potential environmental reservoirs of TYLCV and SLW. Each survey consisted of a collection of 300 random leaf samples from a designated area delimited by 20 rows and eight trellis panels of tomato, each 3–4 m in length. Except for sites 360 and 376, only 200 samples were collected. The total number of plants present in the designated survey area was approximately 1500 to 2000. Within the same designated area, whitefly was collected from 80–125 sampling points using a vacuum method. Each sampling point was equivalent to an area of four tomato leaflets . Crops were only monitored for TYLCV as there are no other SLW-vectored viruses affecting tomatoes in this district.Total nucleic acid extracts (TNAEs) were prepared from tomato leaf samples using the Qiagen Biosprint Kit as per manufacturers’ instructions and from whitefly samples using the method by . Both plWeather data from the nearby Australian Bureau of Meteorology stations was sourced for the study period. The locations are shown in


Roseburia intestinalis is an anaerobic, Gram-positive, slightly curved rod-shaped flagellated bacterium that produces butyrate in the colon. R. intestinalis has been shown to prevent intestinal inflammation and maintain energy homeostasis by producing metabolites. Evidence shows that this bacterium contributes to various diseases, such as inflammatory bowel disease, type 2 diabetes mellitus, antiphospholipid syndrome, and atherosclerosis. This review reveals the potential therapeutic role of R. intestinalis in human diseases. Patients with inflammatory bowel disease exhibit significant changes in R. intestinalis abundance, and they may benefit a lot from modulations targeting R. intestinalis. The data reviewed here demonstrate that R. intestinalis plays its role in regulating barrier homeostasis, immune cells, and cytokine release through its metabolite butyrate, flagellin and other. Recent advancements in the application of primary culture technology, culture omics, single-cell sequencing, and metabonomics technology have improved research on Roseburia and revealed the benefits of this bacterium in human health and disease treatment. Roseburia spp. have been brought to the fore because of their novel role in modulating the gut microbial ecology, immune responses, and the development of human disorders , all of which produce short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate  of the total microbiota   can convert pyruvate to acetyl-CoA  promotes the growth of R. intestinalis by inhibiting reactive oxygen species (ROS) signaling and induces resistance in mice with dextran sulfate sodium (DSS)-induced colitis  . R. intethe diet . β-mannay manner . The groetyl-CoA . In addietyl-CoA . These d colitis . Colonic colitis . Severalbacteria . This phtic role .R. intestinalis  on the Evaluation of Probiotics in Food issued in 2002, probiotics are viable microorganisms in dietary supplements that, when consumed at certain levels, stabilize the gastrointestinal tract microflora and confer health benefits to the consumer. In addition to our attempts to expand knowledge about stinalis Figure 1R. intestinalis, as a digestive tract resident, plays a role in metabolic reprogramming, immune activation, and in sustaining the gut barrier. Notable prominent features of inflammatory bowel disease (IBD) [encompassing Crohn’s disease (CD) and ulcerative colitis (UC)] include microbiota dysbiosis, impaired innate immunity, and extensive tissue damage (mainly in the colon). Global cohorts  is a colonic transit and sensory disorder characterized by constipation, diarrhea, or mixed subgroups. Results from 16S ribosomal RNA (rRNA) sequencing and fluorescence in situ hybridization (FISH) analysis in a French cohort showed that constipated-IBS (C-IBS) patients had lesser Roseburia abundance than did the controls  through intrinsic enhancer conserved non-coding sequence 1 (CNS1)  and promoted the differentiation of Tregs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis (via butyrate stimulation can bind the aryl hydrocarbon receptor (AhR) in regulatory B cells (Bregs), inducing suppressive effects  . The mec1 (CNS1) . In view colitis . Recent  effects . In memo effects . It is presponse . Evidencresponse . Notablyresponse . Additioresponse . ConsequR. intestinalis in decreasing the secretion of the macrophage-derived oncostatin M (OSM) and maintaining intestinal mucosal permeability to alleviate DSS-induced colitis ] ] . Throughll lines . The aboorted by .R. hominis potentially strengthens the function of the gut barrier and enhances the expansion of the population of Tregs, possibly via flagellin/Toll-like receptor 5 (TLR5) signaling. Also,  via p38/STAT1 signaling, exhibiting an anti-inflammatory role  and compared the results to other glycolysis lipolytic and amino acid metabolic enzymes (unpublished). In another recent project in 2019, we aimed to investigate the balancing mechanism between intracellular and extracellular tryptophan metabolism. The results of the study demonstrated that intracellular IDO1-mediated tryptophan metabolism potentially altered R. intestinalis flagellin–TLR5 signaling. Also, extracellular tryptophan metabolic indoles were suggested to activate ILC3 and IL-22 production via the AhR. Notably, the combined effect may induce colonic and systemic anti-inflammatory effects by immunometabolism. More and more evidence had accumulated to support the potential role the gut–brain axis plays in digestive disorders. For example, R. intestinalis may function in the modulation of the gut–brain axis by reducing the level of colonic 5-hydroxytryptamine (5-HT), inhibiting the expression of glial fibrillary acidic protein (GFAP), and alleviating the depression-like behaviors in colitis model mice  patients, Forbes et al. found a decreased on model . In addioperties . Notablyolvement . Howeverpatients .R. intestinalis and the autoantigen β2-glycoprotein (β2GPI)  was significantly elevated in APS patients and was correlated with anti-β2GPI IgG autoantibodies. Meanwhile, R. intestinalis gavage could trigger an autoimmune pathology in susceptible mice , researchers have discovered cross-reactivity between non-orthologous mimotopes expressed by  (β2GPI) . Besidesble mice . HoweverRoseburia spp. are a critical butyrate-producing bacteria cluster. Several researchers have reported that the potential role of butyrate is by inhibiting histone deacetylase (HDAC) or interacting with G protein-coupled receptors (GPCRs) such as free fatty acid receptors 2 (FFAR2) and 3 (FFAR3) in the control of body weight and insulin sensitivity   reported lower R. intestinalis abundance  enrichment analysis, researchers have demonstrated that intestinal microbiome dysbiosis alters the commensal remolding and shifts the nutritional metabolism. Accumulating evidence reveals the tight association of butyrate with glucose homeostasis, insulin resistance, and appetite . Metabolsitivity . Butyratsitivity . To dates (T2DM) Table 2.patients . These rpatients . Howeverbundance . Furtherria spp. . Taken tria spp.  recruiterameters . These pRoseburia, transmit signals to the colonic glia to stimulate the IL-22 production of ILC3 mediated by glial neurotrophic factors  and controls showed that Roseburia was significantly more abundant in controls than in PD patients  patients than in the matched healthy group   . TherefoR. intestinalis can infiltrate the gut barrier and circulate in the artery and the vein. As such, it is imperative to investigate the effects of R. intestinalis in circulatory diseases  hypertensive rat model  but enrichment in R. intestinalis correlated with low nadir CD4+ T-cell counts, which could predict gut dysbiosis in HIV (Roseburia abundance was reported in active tuberculosis (TB) patients, and Roseburia promoted TB pathophysiology by enhancing the anti-inflammatory milieu in the host , divergent results were found , hepatocellular carcinoma, pancreatic tumor, and cervical cancer. Therefore, the microbiota can serve as early diagnostic biomarkers to guide precise cancer treatment. A previous investigation by  Austria . Similar Austria . After are found . It is ncontrols . A mix ounogenic . A singlt of CC4 . This seRoseburia spp. in the gut flora of model rats compared to that of the control group (Acute respiratory distress syndrome (ARDS) is an acute lung injury that occurs mostly following an infection, chemical airway burn, or other factors. ARDS is characterized by a disruption of the alveolar epithelial and endothelial barrier, inflammatory effusion, ventilation defect, and severe respiratory failure. Intestinal microbial dysbiosis may aggravate ARDS. A previous study conducted using an acute lung injury rat model  demonstrated a higher diversity index and a lower number of ol group .Roseburia  is comorbid with metabolic and cardiovascular complications, and most patients can progress into end-stage renal disease. In addition, a deteriorated internal environment frequently accompanies an impaired gut barrier and low-grade inflammation. CKD patients have been shown to harbor shrunken percentages of beneficial microbes, including oseburia . In anotstatin C . Some st disease , and relRoseburia spp., especially R. intestinalis. Nearly all the data demonstrate a probiotic role of R. intestinalis in preventing infection and in relieving and reversing the pathological process. Notably, R. intestinalis has displayed a beneficial role in different modes, such as butyrate, supernatant, flagellin, and organism effect. In combination with other emerging evidence, findings from our research group have revealed the effect of R. intestinalis on Tregs, ILC3, Th17, and macrophages and the stimulation of anti-inflammatory cytokines . There is evidence that different technologies have been applied to modulate R. intestinalis-associated disease treatment  internalized R. intestinalis, and the magnetic field can be directed both in vitro and in vivo  81970494 was grant to XW and 81800500 to YY.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The present study is aimed at investigating the mechanical behaviour of fabricated synthetic midthoracic paediatric spine based on range of motion (ROM) as compared to porcine spine as the biological specimen. The main interest was to ensure that the fabricated synthetic model could mimic the biological specimen behaviour. The synthetic paediatric spine was designed as a 200% scaled-up model to fit into the Bionix Servohydraulic spine simulator. Biomechanical tests were conducted to measure the ROM and nonlinearity of sigmoidal curves at six degrees of freedom (DOF) with moments at ±4 Nm before the specimens failed. Results were compared with the porcine spine . The differences found between the lateral bending and axial rotation of synthetic paediatric spine as compared to the porcine spine were 18% and 3%, respectively, but was still within the range. Flexion extension of the synthetic spine is a bit stiff in comparison of porcine spine with 45% different. The ROM curves of the synthetic paediatric spine exhibited nonlinearities for all motions as the measurements of neutral zone (NZ) and elastic zone (EZ) stiffness were below “1.” Therefore, it showed that the proposed synthetic paediatric spine behaved similarly to the biological specimen, particularly on ROM. Human adult and animal cadaveric spines such as porcine, sheep, baboon, and calf are commonly used in biomechanical investigation –5. Over The main challenge in developing the paediatric biomechanical analyses was limited information of paediatric experimental data to enable a direct comparison with the finite element model. Recently, a few studies were reported on the use of paediatric human cadavers to investigate the paediatric biomechanical response , 14. OuyDevelopment of a synthetic paediatric spine is essential to investigate the mechanical behaviour of paediatric cases such as scoliosis. The common surgical procedure among paediatric cases is early onset scoliosis surgical treatment, and studies on the effect and accuracy of various paediatric spinal instrumentations of scoliosis normally were conducted only using FE studies, animal spines, or postoperative studies that required years of observation , 16, 17.The first step in synthetic paediatric spine fabrication was the development of physical paediatric spine model. Since the actual physical size of paediatric model was relatively small to be tested with the MTS Bionix Servohydraulic spine simulator, a scaling process was considered. To the author's knowledge, no data on physiological ROM of human paediatric spine exists, particularly in the thoracic region, and thus, it is essential to generate an experimental protocol by using biological specimens before ROM of the synthetic spine was determined.Another important factor that was considered while developing the synthetic paediatric spine was the actual size of human paediatric spine. Assuming that size of the paediatric spine is 100%, the size of adult spine is normally scaled up to 141%, and the size of porcine spine is larger than an adult spine by an average difference of 50% , 28. TheA physical model of paediatric vertebra was purchased from Sawbones  for all regions, and these vertebrae represent the anatomical dimension of a juvenile group (8 to 9 years old). Since this study focused on T4-T8, five individual vertebrae were scanned in three-dimension (3D) before being scaled to 200% in a selective laser sintering (SLS) machine to fabricate the prototype.The materials to fabricate the synthetic spine were divided into three main components, which were vertebra, intervertebral disc, and spinal ligaments. All materials used in the synthetic paediatric spine were structurally and mechanically close to human data. This was to ensure that the final product (synthetic paediatric spine) could replicate human behaviour. Details of analysis to select the material for each component of spine are available in previous author's publications, namely, for vertebra , interveThe paediatric synthetic spine was fabricated as a single functional spinal unit (FSU), consisting of two vertebrae, an intervertebral disc, and associated ligaments. The process started with embedding the cortical around the trabecular structure. Next, the disc was attached within the two vertebrae by using the “spinous processes” natural structure as reference. The next process was to mould the spinal ligaments within the posterior elements and attach the anterior longitudinal ligament (ALL) and posterior longitudinal ligament (PLL) within the vertebral body. Finally, the vertebral body was covered with sheet wax. All materials used in the synthetic paediatric spine were geometrically and mechanically close to human data. The fabrication process flow is summarised in To provide an indication of whether the materials selected to fabricate the synthetic paediatric spine could mimic human spine movement or not, a series of experiments were carried out for both porcine spine and synthetic paediatric spine.Six porcine spines from 6 months to 7 months old were provided from a local abattoir. The breed was a cross Saddleback with Gloucester porcine. Average weight of spines used was 82.34 kg (±4.9 kg). The full spines were freshly dissected into single FSUs  with three specimens for each FSU, as shown in Four FSUs of synthetic paediatric spine from T4 to T8 were prepared based on the fabrication process mentioned in These experiments were conducted by using MTS Bionix Servohydraulic system spine simulator. Specimens were fixed at its natural position in the spine simulator before testing, as shown in All specimens were tested to obtain flexion, extension, right and left lateral bending, and right and left axial rotation by using the MTS Bionix Servohydraulic spine simulator under similar experimental procedures developed prior to the porcine spine test. To observe the performance of synthetic paediatric spine, three specimens were tested until failure by using a pure moment of ±1 Nm (0.1 deg/sec) for all six DOF with an increment of ±1 Nm. Results from these three specimens showed that the specimens failed at ±5 Nm, whereby the disc started to detach from the vertebrae. Therefore, an assumption was made that the valid ROM for the paediatric synthetic spine in this study was at ±4 Nm. The rest of specimens were tested at ±4 Nm with 1 deg/sec rate. All specimens were tested to five cycles, whereby the first two cycles were considered as the precycle and results were determined at the fifth cycle.ROM was determined from the sigmoidal curve for each loading direction from the fifth cycle: flexion, extension, right and left lateral bending, and right and left axial rotation. The typical curve for each loading direction is shown in Results collected from synthetic paediatric spine test were plotted in the sigmoidal curve to observe if any nonlinearity existed in the ROM. The nonlinearities or sigmoidal patterns were essential to prove that the synthetic paediatric spine exhibited a viscoelastic behaviour, which is normally found in the biological specimens. The nonlinearities of graphs were observed for all specimens, as it was the key parameter to determine the performance of synthetic spine as compared to the biological specimens. The value of S1/S2 was expected to be lower than 1.0 to prove that the curve was a nonlinear curve, whereby the smaller the value, the stronger the sigmoidicity.The ROM data for each FSU at ±7.5 Nm moment is summarised in As for ROM at moment of ±4 Nm, it increased from flexion extension to lateral bending and axial rotation, except for T5-T6. The differences between each FSU in each DOF were only around 20%, except for T5-T6. Data indicated that T5-T6 in axial rotation was the stiffest as compared to other FSUs and DOF. The ROM data for each FSU at ±4 Nm moment is summarised in Variables of interest were the ROM and value of S1/S2, as summarised in The second variable was ROM of each FSU, whereby the pattern that emerged for ROM values showed distinct differences between FSUs. The results can be divided into two groups, which were the upper FSUs (T4-T5 and T5-T6) and lower FSUs (T6-T7 and T7-T8) in all six DOF. The upper FSUs and lower FSUs were within the same range for all six DOF. The percentage differences within upper FSUs and lower FSUs were more than 50% for all six DOF. Flexion/extension was the stiffest motion, followed by lateral bending and axial rotation. Despite differences between FSUs, the pattern emerged similar to the pattern showed in porcine spine, whereby the ROM increased from flexion/extension to axial rotation.The biomechanical analysis of a spine was normally carried on a single FSU. Despite testing a small segment of the spine, it can exhibit the characteristics of the entire spine. Due to limited information on the physiological ROM of paediatric spine, the porcine spine was an essential substitute to guide in biomechanical testing. The physiological ROM included were flexion and extension, left and right lateral bending, and left and right axial rotation. The series of tests were conducted on porcine spines from T4 to T8 on a single FSU under ±7.5 Nm moments at all six DOF. The ROM was measured for all six DOF at ±7.5 Nm moments and was directly compared with a previous study on porcine spines by Wilke et al. , since tIn The average of all FSUs for the midthoracic region (T4-T8) is summarised in Since no data is available on ROM of human paediatric spine, further analysis was required to compare the porcine ROM with human adult ROM from White and Panjabi under the same moment . The ROMThe crucial element in testing synthetic paediatric spine was to ensure that the plotted curve showed nonlinearities to replicate the viscoelastic behaviour of soft tissues in human spine. Therefore, the first parameter was to determine the ratio of EZ stiffness (S1) to NZ stiffness (S2). In The nonlinear behaviour in ROM was a result from both soft and hard tissues. The lateral bending exhibited nonlinear curves with a ratio closer to 0, suggesting that the materials selected as synthetic intervertebral disc replicated the human behaviour. The lateral bending movement was dependent on the nonlinearity of intervertebral disc as the facet joints made less contact with each other. As for the axial rotation and flexion/extension, the nonlinearity curves measured were closer to 1, which suggested that the ROM tended to be more linear. These movements involved facet contacts that tended to be stiffer due to stiffness of the bone. This was potentially caused by assuming that the facet joints had the same material properties as spinal ligaments.The ROM of porcine was compared to synthetic paediatric spine at ±4 Nm moments. As the size of synthetic paediatric spine (200%) and porcine spine (190%) was 10% different, the average ROM was expected to differ, but was still within the same range. Two assumptions were made in the comparative analysis. The assumptions were that the relation between specimen size and ROM was not linear, and that the synthetic paediatric spine was fabricated by using synthetic material, which did not necessarily exhibit all the behaviour of biological soft tissues. Theoretically, the synthetic materials used in the synthetic paediatric spine were supposed to allow wider movement as compared to the human adult spine. Therefore, the ROM of synthetic paediatric spine was expected to be within the same range as porcine spine, because the porcine ROM was larger than the human adult ROM .Generally, porcine spine ROM was more flexible as compared to synthetic paediatric spine in all six DOF, with a larger difference in flexion/extension by 45%. The flexion and extension was expected to be lower in the synthetic paediatric spine as compared to the porcine spine because the experimental data of all synthetic paediatric spines were relatively lower as compared to other ROMs. The difference found for synthetic paediatric spine and porcine spine for lateral bending was 18% while it was only 3% in axial rotation.The average ROM in lateral bending and axial rotation of synthetic paediatric spine were within the acceptable range with porcine spine while flexion/extension differed by 45%. One of the research limitations is the simplified shape of intervertebral disc for the synthetic paediatric spine, which potentially caused a significant difference in flexion/extension. However, synthetic paediatric spine ROM exhibited a nonlinear curve for all six DOF, suggesting that the ROM measured was acceptable because the synthetic paediatric spine demonstrated a viscoelasticity behaviour that existed in human soft tissues. From the comparative analysis between the synthetic paediatric spine and porcine spine, the synthetic paediatric spine developed in this research mimicked the behaviour of biological specimen. Future works will consider using finite element analysis of paediatric spine to investigate the correct loading required in the biomechanical testing to obtain paediatric ROM.The limitations in this study are there is no data of paediatric ROM to enable a direct comparison and the synthetic paediatric spine has to be scaled up to 200% from the actual size to fit the fixation holder in the spine simulator. Although it was a scaled-up model, the morphology of the paediatric vertebra was still maintained.In the present study, fabricated synthetic paediatric spine in FSU unit was tested with a MTS Bionix Servohydraulic spine simulator to obtain the ROM in flexion, extension, lateral bending, and axial rotation. Overall, the ROM curves of synthetic paediatric spine exhibited nonlinearities as all measurements of NZ and EZ stiffness were below than 1. The ROM was then compared with the porcine spine for comparative analysis by using a comparable size model at ±4 Nm moments. The porcine spine ROM was more flexible than synthetic paediatric spine in all DOF, with a difference of 45% in flexion/extension, while the lateral bending and axial rotation of synthetic paediatric spine were in good agreement with the porcine spine, with differences of 18% and 3%, respectively. The difference in flexion/extension was potentially due to the simplified design of synthetic intervertebral disc, as it did not reflect the unique shape within the vertebral body for each individual FSU. The results presented in this research showed that the fabricated synthetic paediatric spine had nonlinearity characteristic in all DOF. The synthetic paediatric spine ROM was acceptable as compared to the porcine spine at ±4 Nm moments, specifically in lateral bending and axial rotation. Therefore, the fabricated synthetic paediatric spine particularly in thoracic region in this study can mimic the biological ROM. It could potentially be used as replacement of paediatric spine for biomechanical research that is related to spine deformity.


The objective of this study was to compare growth performance, carcass traits and meat quality in young bulls, steers and heifers produced by crossing Limousin bulls with Holstein-Friesian cows, fattened semi-intensively and slaughtered at 18 months of age.musculus longissimus thoracis were collected to determine the proximate composition and quality of meat.Thirty-one young calves were reared in a conventional production system, and were fed milk replacer, hay and concentrate. At 6 months of age, the animals were divided into groups based on gender, and were fed a total mixed ration composed of grass silage, concentrates I and II in a semi-intensive production system. At the end of the fattening period (18 months), the animals were slaughtered, carcass quality was evaluated, and samples of Bulls were characterized by the highest percentage share of the most valuable cuts in the carcass, and three-rib sections from bull carcasses had the highest lean meat content with low intramuscular fat content (0.93%). No significant differences in carcass conformation, dressing percentage or the percentage share of round in the right half-carcass were found between bulls vs. steers and heifers. Heifers and steers had higher carcass fat content than bulls, which had a positive influence on the sensory properties of beef. In comparison with the meat of bulls, the meat of steers and heifers was characterized by more desirable physical properties and sensory attributes .Under the semi-intensive production system, heifers and steers had higher carcass fat content than bulls, which had a positive effect on the sensory properties of beef. Bulls are better suited for intensive systems, which contribute to improving the quality of their meat. The results of this study may encourage producers to breed steers and heifers for beef. The growth performance and carcass attributes of cattle are influenced by gender  ,2. FemalThe aim of this study was to compare growth performance, carcass traits and meat quality in young bulls, steers and heifers produced by crossing Limousin (LM) bulls with Holstein-Friesian (HF) cows, and slaughtered at the same age.3, 50,000 IU; vitamin E, 1,000 mg; dl-alpha-tocopherol, 909.10 mg. TMR, administered from a self-propelled feed cart , was delivered to feeding stations twice daily (at 8:00 am and 4:00 pm). The animals were fattened until 18 months of age. The study was conducted in 2013 through 2014 upon the approval of the Local Ethics Committee for Animal Experimentation (decision No. 121/2010).The experiment was performed at the Agricultural Experiment Station in Bałcyny , on 31 animals, including 10 young crossbred bulls, 10 steers and 11 heifers, produced by crossing HF cows with LM bulls. Calves of known origin, which were purchased at 2 or 3 weeks of age, underwent a 7-day quarantine period. Bloodless castration of 10 bulls was carried out using a rubber elastrator. The calves were kept in a group pen. They were fed milk replacer from automatic feeders, hay and concentrate, followed by grass silage. At 6 months of age, the animals were divided into groups based on gender, and were placed in free-stall group pens in a fattening facility. After a 30-day adaptation period, the animals were fed a total mixed ration (TMR) composed of grass silage, concentrate I (to body weight of 300 kg) and concentrate II (at body weight above 300 kg) in a semi-intensive production system . The proThe animals were weighed to the nearest 0.5 kg at the beginning (180 days) and at the end of the fattening period. Average daily gains were calculated. Upon reaching the slaughter age, the animals were transported over a distance of 90 km to the abattoir where they were kept in lairage for 15 to 20 hours prior to slaughter, in individual boxes with free access to water. The animals were stunned, slaughtered, dressed, and halved along the spine into two half-carcasses that were then chilled for 96 hours at 4°C. Electrical stimulation was not applied to the carcasses. Half-carcasses were weighed to the nearest 0.5 kg on an automated on-line scale (hot carcass weight [HCW]), and conformation and fat cover were evaluated based on the EUROP system criteria by a trained grader. The protocol for animal research was approved by the Ethics Committee of the University of Warmia and Mazury in Olsztyn. All slaughter and post-slaughter processes were carried out in accordance with the current meat industry regulations [Carcass dressing percentage (percentage ratio of carcass weight to live body weight at slaughter) was calculated. Ninety-six hours post mortem, three-rib (10th to 12th rib) sections were sampled from the right half-carcasses .m. longissimus thoracis (LT) was outlined on wax paper, between the 9th and 10th thoracic vertebrae, and was measured with a planimeter.The surface area of Half-carcasses were divided into primal cuts and five most valuable cuts, passing through anatomical points of the half-carcass, i.e. shoulder (the upper portion of the front leg without the shoulder cartilage), fore ribs , best ribs , loin  and round of beef , were weighed and their percentage shares of the right half-carcass were estimated.Three-rib cuts were dissected, and the percentage content of soft tissues  and bones was determined.2 and impermeable to H2O. After color measurements, each meat sample was divided into two portions: the first portion was used to determine the proximate chemical composition and physicochemical properties of meat, and the other portion was used to evaluate the sensory attributes of meat.During carcass dressing, LT samples were collected from the right half-carcasses to evaluate beef quality. Meat samples weighing approximately 300 g were packaged in polyamide/polyethylene (PE) vacuum bags at an ambient temperature of around 4°C, under standard industrial conditions. Meat color was evaluated immediately in the laboratory, based on the values of CIELAB coordinates, L*, a*, and b* . Color sThe analysis of the proximate chemical composition of meat included the determination of dry matter, total protein, crude fat and ash, according to the procedure proposed by Wajda et al . The folTo evaluate the sensory properties of beef, 200 g samples were cut out across the muscle fibers, and were cooked in a 0.6% NaCl solution (meat to solution weight ratio of 1:2) at a temperature of 96°C (±2°C). Pasteurization was carried out until the temperature inside the sample reached 75°C. The samples were evaluated based on Polish Standard . The senThree cattle groups were analyzed: bulls (n = 10), steers (n = 10), and heifers (n = 11). The data were processed statistically by analysis of variance (ANOVA) and Tukey’s honest significant difference test at a significance level of 5%. All calculations were performed with the use of Statistica 10 software Semi-intensive feeding was reflected in the fattening performance of bulls, steers and heifers . After 1The slaughter value of cattle and carcass quality are related to the percentage share of cuts with high market value in the carcass. According to Choroszy et al , beef caTissue composition is another determinant of beef carcass quality . SignifiAn analysis of the proximate composition of LT revealed that gender had no effect on the ash and total protein content of LT, although such correlations were observed by Rotta et al . Ash is The ability of muscles to hold water (water-holding capacity) is primarily determined by their pH. As the pH of beef increases, its water-holding capacity and the rate of heat transfer increase as well . In the Studies investigating trends in beef production should focus not only on improving slaughter value and carcass traits, but also the quality of beef so as to meet rising consumer expectations. Consumer research conducted until the 1990s revealed that tenderness was the most important attribute driving consumer liking. However, more recent studies have shown that as overall tenderness improved and tenderness variation decreased, flavor has become a more important driver of beef consumer liking. In general, as long as tenderness and juiciness are at acceptable levels, flavor is the main driver of overall liking ,28. In tRecent research has demonstrated that tenderness evaluation by untrained consumers is a better procedure for assessing the sensory properties of beef, compared with evaluation by trained consumers or instrumental measures . The iniUnder the semi-intensive production system, heifers and steers had higher carcass fat content than bulls, which had a positive influence on the sensory properties of beef. The too low IMF content of meat from bulls (0.93%), which affected its sensory properties, was associated with the diet. Bulls are better suited for intensive systems than steers and heifers. A higher proportion of concentrate in the ration could have a beneficial influence on the fattening performance and carcass characteristics of bulls. Beef from steers and heifers can meet rising consumer expectations because it is characterized by more desirable physical properties and sensory attributes  than beef from bulls. The results of this study may encourage producers to raise steers and heifers for beef.


The United Kingdom National Institute for Health and Care Excellence (NICE) released its guidance on ‘Hysteroscopic mechanical tissue removal (hysteroscopic morcellation) for uterine fibroids on 25 August 2021  . BSGE inAs emphasised in the BSGE feedback the most serious risks associated with hysteroscopic myomectomy are uterine perforation and fluid overload and the prevalence of these complications are similar during mHTR and traditional electrical fibroid resection procedures. Hysteroscopic resection of fibroids has been in prac- tice since approximately 1985 and its safety and efficacy as a simpler alternative to abdominal myomectomy or hysterectomy have been widely accepted. However, hysteroscopic fibroid resection procedures require a high degree of surgical expertise for safe and complete removal of submucosal fibroids. As highlighted by Franchini et al  comparatHistorically, the NICE guidance on mHTR made an unfortunate start. In 2014, shortly after the release, the first guideline was quickly withdrawn at the height of the crisis on laparoscopic power morcellation, before the guideline was revised and reinstated in 2015. The current NICE guideline still states that there is a ‘theoretical risk of dissemination of malignancy with hysteroscopic morcellators’. This concern is somewhat related to the fact that similar terminology is used for ‘laparoscopic’ and ‘hysteroscopic’ morcellators. mHTR systems do not ‘morcellate’ the tissue. As Franchini et al.  brings t


As obligate intracellular parasites, viruses are intimately interconnected with their host cells. Virus–host cell interactions allow viruses to exploit cells for their own purposes, but they also provide a means for the host cell to combat virus infection. This close connection between host and viral processes means that the scientific fields of cell biology and virology have often inspired each other.In particular, many discoveries in cell biology have been made possible by the study of viruses, while, at the same time, our fundamental understanding of the virus life cycle is inherently rooted in the principles of cell biology. By examining cellular responses to infection, we can gain insights regarding the mechanisms associated with the restriction of virus infection or, in cases where control is ineffective, pathogenesis. Such knowledge is a prerequisite for the successful modulation of these responses to develop host-directed therapies for the control of viral infections. Furthermore, from a practical point of view, virus–host cell interactions also provide important targets for the development of indirectly acting antivirals, which have a reduced likelihood to develop resistance due to their reliance on host cell components.Cells compiles both review papers discussing the current state of our knowledge regarding important emerging themes related to virus–host cell interactions, and research articles reporting new discoveries in this scientific area. These publications cover various aspects of the virus life cycle, from virus entry, uncoating, and virus replication in specialized replication compartments, all the way to virus particle production. They also touch on the complex interplay of viruses with the immune system, and current topics such as the modification of viral RNAs.This Special Issue of One of the first interactions of a virus with its host cell is during the entry process, which is generally facilitated by the interaction of a virus surface protein with a cellular receptor, and sometimes by additional interactions with cellular attachment factors, in order to facilitate virus uptake. Here, a mechanism that is increasingly recognized as being exploited by diverse virus families is apoptotic mimicry, which in its canonical form involves the exposure of phosphatidylserine in the outer leaflet of the viral membrane. This exposed phosphatidylserine can then be recognized by host cell proteins, such as those of the T-cell immunoglobulin and mucin domain (TIM) family. Kirui et al.  demonstrIn a second study on virus entry, but from the perspective of the role that virus entry receptor expression can play in directing infection outcome in different tissues, DeBuysscher et al.  show thaAfter entry, the next hurdle that many viruses have to overcome in order to establish a successful infection is the uncoating of the virus genetic material to facilitate its release. In a featured review on Influenza virus uncoating, Moreira at al.  discuss For viruses that replicate in the cytoplasm, genome replication and viral transcription are increasingly being appreciated to take place in specialized replication organelles. For positive-strand RNA viruses, these are predominantly membranous structures. In contrast, for a growing number of negative-strand RNA viruses, viral RNA synthesis has been shown to be localized in inclusion bodies that are not delineated from their surroundings by membranes. Two reviews highlight the progress that is being made in understanding both of these types of replication organelles. Nguyen-Dingh and Herker  focus onWithin these replication organelles, transcription leads to the generation of viral mRNAs. However, what has remained underappreciated in virology is that, in many cases, these mRNAs can be modified by the addition of methyl groups by host cell proteins. In the second featured review of this Special Issue, Courtney  providesFinally, in order to complete their life cycle, viruses have to exit their host cell, and this process is often intimately interlinked with the subversion of cellular host factors. In the case of non-segmented negative-sense RNA viruses, particle production is frequently driven by a dedicated viral matrix protein. Focusing on the Ebola virus matrix protein VP40, Paparisto et al. show that the process of particle production is inhibited by the cellular protein HECT and RCC1-like containing domain 5 (HERC5) . HoweverOf course, host–pathogen interactions involved in antiviral control not only occur at the level of specific antiviral cellular factors or cellular antiviral responses, but can also include a broader range of interactions with the immune system. This is highlighted in a comprehensive review by Muralidharan and Reid, in which they illuminate the complex roles of neutrophils during arbovirus infections . Using eStaphylococcus aureus on the expression of bacterial virulence factors as well as on the infected host, particularly regarding its cytokine response and the integrity of the alveolar-capillary barrier. This work provides mechanistic support for the clinical observation that severe influenza infections are frequently complicated by bacterial coinfections.An equally complex but currently underappreciated topic is that of pathogen–host interactions in the context of coinfections involving several disease agents, and particularly co-infections of viruses and bacteria. In this context, a study by Nickol et al.  demonstrOverall, this Special Issue provides examples of the crucial role that virus–host cell interactions play in the biology of a diverse range of viruses, and highlights the importance of better understanding such interactions in order to be better able to combat virus infections and the mechanisms that contribute to pathogenesis and disease.