Objective: The presence of focal lesion (FL) after a severe traumatic brain injury is an important factor in determining morbidity and mortality. Despite this relevance, few studies show the pattern of recovery of patients with severe traumatic brain injury (TBI) with FL within one year. The objective of this study was to identify the pattern of recovery, independence to perform activities of daily living (ADL), and factors associated with mortality and unfavorable outcome at six and twelve months after severe TBI with FL. Methodology: This is a prospective cohort, with data collected at admission, hospital discharge, three, six, and twelve months after TBI. RESULTS: The study included 131 adults with a mean age of 34.08 years. At twelve months, 39% of the participants died, 80% were functionally independent by the Glasgow Outcome Scale Extended, 79% by the Disability Rating Scale, 79% were independent for performing ADLs by the Katz Index, and 53.9% by the Lawton Scale. Report of alcohol intake, sedation time, length of stay in intensive care (ICU LOS), Glasgow Coma Scale, trauma severity indices, hyperglycemia, blood glucose, and infection were associated with death. At six and twelve months, tachypnea, age, ICU LOS, trauma severity indices, respiratory rate, multiple radiographic injuries, and cardiac rate were associated with dependence. Conclusions: Patients have satisfactory functional recovery up to twelve months after trauma, with an accentuated improvement in the first three months. Clinical and sociodemographic variables were associated with post-trauma outcomes. Almost all victims of severe TBI with focal lesions evolved to death or independence. Traumatic brain injury (TBI) occurs when a force transmitted directly to the brain results in pathophysiological damage and dysfunction that begins at the time of the accident and lasts for days to weeks . TBI is The consequences of the injury remain beyond the acute phase of TBI, extending and changing for a long time after the traumatic event ,10. The Thus, the recovery of patients with severe TBI is considered a complex and dynamic process, which requires early identification of consequences during the critical period of hospital stay and monitoring over time to prevent and manage clinical problems . ReferriTo assess other aspects of recovery after TBI, in addition to the Glasgow Outcome Scale Extended (GOS-E) and the Disability Rating Scale (DRS), which are already widely applied , some stKnowing the recovery pattern, ADL, and IADL of victims with severe TBI with focal lesions, and the factors associated with this outcome are important to identify the prognosis of these patients up to one year after TBI, provide resources for comprehensive care for these patients, evaluate the care provided, direct treatment to minimize the disabilities caused by TBI, guide the family as to the probable prognosis, in addition to contributing to the development of systematic assistance aimed at the rehabilitation and reintegration of victims into society .Other studies also show a progressive improvement in recovery from hospital discharge up to ten years after TBI, however few of them have addressed long-term functional recovery and independence to perform ADL and IADL in patients with severe TBI with focal injury ,22,25. IThis is an observational prospective cohort study with patients with severe TBI and predominantly focal lesions such as contusion, subdural hematoma (SDH), epidural hematoma (EDH), and intraparenchymal hemorrhage.Severe TBI was considered as admission GCS ≤ 8. Traumatic subarachnoid hemorrhage (SAH) with concomitant focal lesion were also included. Those lesions can be the result of focal damage, but it can often be seen in more diffuse vascular lesions. Patients with exclusive SAH were excluded. There were five time points for data collection: during hospitalization, at hospital discharge, and three, six, and 12 months after the event.This study was carried out in the largest trauma hospital in Latin America. Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP) has more than 50 surgical rooms and 1000 inpatients capacity, with a dedicated neurotrauma and critical care unit, located in the state of São Paulo, Brazil.Subjects with GCS ≤8 at hospital admission and between 18 years and 60 years of age were selected for the study. Participants diagnosed with severe TBI with focal lesions were included in the research. The following criteria were used to exclude patients: initial hospital treatment after six hours of the traumatic event, transfer from other hospitals, previous diagnosis of TBI, exclusive diffuse lesions or with normal CT, presence of psychiatric disorders or chronic pathologies  and with lesions in the spinal cord region with severity ≥ 3, according to the AIS classification . PatientThe institutional ethics committee  approved the study and waived the need for patient informed consent. This study was carried out following the recommendations of the Declaration of Helsinki II .Clinical variables related to trauma, hospitalization, and outcomes were recorded for each participant and prospectively collected, including mortality at 14 days, 6 months and 12 months.The clinical variables related to trauma surveyed at hospital admission were: age, reported alcohol intake; Glasgow Coma Scale (GCS) ; OrotracThe variables identified during hospitalization related to hospitalization were: time sedated while mechanically ventilated, length of stay in the intensive care unit (LOS ICU), presence of any infection that required active treatment, presence of intracranial hypertension (ICH) assessed by clinical and radiological findings and neurosurgical treatment .Trauma indices assess the global severity of injuries in individuals after a traumatic event. The Injury Severity Score (ISS) scales were used for the main article. Data for the following scales are available in the The ISS is an anatomical trauma index that assesess the severity of injuries from the sum of squares of the 3 highest Abbreviated Injury scores Scale (AIS). ISS scores range from 1 to 75, the higher the score, the greater the severity of the injuries.Regarding outcome-related variables, mortality and functional dependence at six and 12 months with GOS-E were used. Due to the severity of TBI and the multidimensional nature of recovery, it was decided to use GOS-E to assess functional dependence. The DRS scale is also available as The GOS-E score ranges from one to eight, being: (1) dead, (2) vegetative state, (3) lower severe disability, (4) upper severe disability, (5) lower moderate disability, (6) upper moderate disability, (7) lower good recovery, (8) upper good recovery. Scores from 1 to 4 were classified as dependent and scores from 5 to 8 as independent .Independence for ADL was assessed using the Katz index and IADL was assessed using the Lawton scale. The Katz Index assesses six ADL functions: bathing; feeding; dressing up; going to the bathroom; getting in and out of bed and maintaining sphincter control . Katz’s Data is presented as mean and standard deviation (SD) for continuous variables, median with IQRs for ordinal variables and count for categorical variables. Shapiro–Wilk test was used to examine normality of distribution of continuous variables. To compare the average of the total value for GOS-E, DRS, Katz Index, and Lawton Scale between time points, the non-parametric Quade test was used. As there was a significant difference between the results of these evaluations, multiple comparisons were made (two-by-two comparisons between times), using the Wilcoxon signed-rank test with correction for multiple comparisons with the Holm–Bonferroni method.t-test for two samples, Wilcoxon-Mann–Whitney test, and Brunner-Munzel test were applied.To identify associations between variables of interest and death outcomes up to twelve months and recovery aspects  at six and twelve months after trauma, comparisons were made between groups of people who died or not, and between those who were dependent or independent at six and twelve months after severe TBI with focal lesions. In these comparisons, Pearson’s Chi-Square or Fisher’s Exact test, Student’s All information collected was stored in a computerized database built using the R 3.4.2 software . For all analyses, a significance level of 5% was considered. The analysis was blindly performed by the author C.P.E.d.S.Between September 2014 and September 2017, 319 patients with GCS ≤ 8 were admitted. Of these, 133 were included based on the inclusion and exclusion criteria. The most frequent injuries were cerebral contusion (29%), subdural hematoma (28%), subarachnoid hemorrhage (20%), and extradural hematoma (16%).Regarding the severity of the trauma, the ISS ranged from 14 to 66, with a mean of 33.17 (SD = 8.785) and a median of 35; the ISS ranged from 14 to 75, with a mean of 53.27 (SD = 15.212) and a median of 57.The mean sedation time was 6.4 days (SD = 7.16). Almost all victims (97%) in this study were admitted to the intensive care unit (ICU). The length of stay in the ICU ranged from one to 71 days. The mean length of stay in the ICU was 13.8 days (SD = 13.42), with a median of 10.5 days. During the hospital stay, 47 patients (35.3%) developed an infection and 18 patients (13%) developed intracranial hypertension.During hospital stay, 63 victims (47%) underwent neurosurgical procedure. Of these, the most frequent procedure was decompressive craniotomy, performed in 84.1% of the patients. Among surgical procedures performed by other specialties, 11 patients (8%) had orthopedic procedures and ten patients (7%) had general surgery procedures. The hospital length of stay varied between one and 187 days, with a mean of 24.78 days (SD = 29.43) and a median of 14 days.At discharge, 50 (61%) patients were classified as having a severe disability and no participant was in a vegetative state. After 12 months, 15 participants were dependent, nine (12%) had severe disability, and 6 participants (8%) had a vegetative state .p < 0.05). There was no statistically significant difference in the period between 6 and 12 months (p = 0.061) after trauma.The results of multiple comparisons indicate that the categorization of GOS-E was statistically different between the periods consisting of discharge and three months, the period between three months and six months, the period of discharge and twelve months, discharge and six months (p < 0.05).For ADLs described in Regarding IADL, Within 14 days after TBI with focal lesions, 40 participants (30%) had died, and 82 patients were discharged. The main cause of death was brain death in 55% of patients, cardiopulmonary arrest in 22.50%. After six months, 19 participants (25%) were classified as dependents according to GOS-E . At 12 months, 15 participants (20%) were classified as dependent .p < 0.001), length of stay in ICU (p < 0.001), GCS (p < 0.001), reports of alcohol consumption (p = 0.029), glycemic alterations (p < 0.01), hyperglycemia (p = 0.039) and the occurrence of infection (p < 0.01). ISS, NISS, and RTS and survival prediction models (TRISS and NTRISS) also showed a statistically significant association with 14-day death (p < 0.005).p = 0.003), length of stay in the ICU (p < 0.001), changes in respiratory rate (p = 0.048), and two or more brain radiographic injuries (p = 0.011) were factors associated with dependence at six months. Similarly, age (p = 0.009), length of stay in the ICU (p < 0.001), changes in heart rate (p = 0.028), two or more brain radiographic injuries (p = 0.001) were factors associated with dependence at 12 months. As for the trauma severity indices, only the NISS (p = 0.026) was associated with dependence at six months, and the NISS (p = 0.002), TRISS (p = 0.019), and NTRISS (p = 0.016) at twelve months.Age (p > 0.05).Due to the different nature of lesion from the patients in our study, Considering that TBI is the main cause of disability and absence from productive activity ,41, therp = 0.006). Research carried out in Latin America with severe TBI showed similar results, with 28% of participants dying during hospitalization, while 36% died in the first six months of the study [We observed in our cohort after severe TBI with focal lesions, 40 participants 30.1%) died within 14 days and 51 participants (38%) within 12 months. Due to the severity of TBI, most participants die within the first few days after the trauma. The main cause of death was brain death in 55% of patients and cardiopulmonary arrest in 22.50%. All those patients were treated in the largest and one of the most important trauma hospital in Latin America and died despite the best possible treatment, including a specialized trauma and intensive care team, early imaging , and immediate surgery, if necessary. Moreover, the high mortality in those patients is also related to the initial very severe injury , DRS (79%), and Katz Index (79%) assessments, while half of the participants were classified as independent by the Lawton Scale (54%).Studies with severe TBI victims have not used repeated measures of ADL and IADL capacity in the first months after trauma to characterize the course of spontaneous remission of the consequences of this injury. For this purpose, the use of functionality scales that seek to cover the global outcome of disabilities, such as GOS, GOS-E, DRS, and the Functional Independence Measure (FIM), allows the assessment of the individual as a whole and integrated into society ,51,52,53In our study, approximately half (54%) of the participants were independent to perform IADL at twelve months after severe TBI. Although the number of patients who underwent treatment with other specialists  varied between 56% at three months to 47% at twelve months, the severity of the injury caused by TBI does not reach the final pattern of recovery and independence to perform more complex activities of daily living in the first twelve months in part of the individuals. This improvement in recovery can persist in some individuals, with varying degrees of intensity, for two to ten years after trauma . A studyPrevious research has shown that sociodemographic and physiological variables are associated with mortality and unfavorable outcome after severe TBI ,62,63,64Surprisingly, two or more brain radiographic injuries were not associated with death within 14 days; however, there was an association between these findings and dependence at six and twelve months. Hilario et al.  observedp = 0.680). Tohme et al. [Secondary injury is a complex process that occurs in the hours and days after primary injury, which encompasses cranial and systemic complications. Matovu et al.  showed te et al. , age, ICe et al. .Despite data from 33.1% of patients being available only after prehospital intubation, respiratory rate was an independent predictor of poor outcome at 6 months in our cohort. Regarding oxygen levels, Volpi et al.  showed tThe present study has several limitations. The major limitation of this study is the absence of records on the clinical conditions in the scene, which limits the identification of factors associated with the TBI outcome. Secondly, the sample of this research included participants from a single institution, a reference center for the care of highly complex cases, bringing restrictions to the generalization of the results. Data for specific scales that evaluate spinal cord lesions were not collected. The correlation found between mortality and sedation may provide limited information because patients with early death cannot have prolonged sedation. Finally, the limited access to rehabilitation resources after discharge  by nearly half of the survey participants can compromise functional improvement and independence for ADL over time. Moreover, specific data for which patient were able to have physical therapy and their outcome would also be an important information and necessary variable to precisely predict long term rehabilitation.Mortality in patients with severe TBI with focal lesion in our trauma reference center in Latin America was high; however, most survivors reached conditions compatible with independent living at twelve months. During this period, the recovery of victims was accentuated in the first three months. Almost all victims of severe TBI with focal lesions evolved to death or independence. There was an improvement in functional capacity by GOE-E in 80% of those evaluated and in ADL performance in 93% of cases. Reported alcohol intake, sedation time, ICU LOS, GCS, trauma indices, hyperglycemia, blood glucose, and infection were associated with death. Tachypnea (RR > 20), age, ICU LOS, NISS, TRISS, NTRISS, two or more brain radiographic injuries, and cardiac rate were associated with dependence at six months and twelve months. This data can help health providers better predict outcomes and provide adequate health treatment.


Hermetia illucens, which has been thoroughly tested for usefulness as feed. This study aimed to determine whether the partial replacement of SBM with defatted H. illucens larvae meal in the diet of laying hens is possible, without a negative impact on performance indices, egg quality, and health.The search for a substitute for soybean meal (SBM) as a feed source in compound feeds has been a significant challenge in the poultry industry. Substitutes with a similar nutritional value and from local sources are desirable. Thanks to changes in European Union law, insects can be used in poultry feed since 2021. This enables the usage of meal from the insect Hermetia illucens larvae meal (HIM) content. The hens in the experimental groups received a diet containing defatted HIM at levels of 5, 10, and 15% , at the expense of a proportionally decreasing content of SBM. During the 12-week experiment, the laying performance, biochemical and redox blood indices, and liver condition were examined. The cholesterol level, fatty acid profile, and malondialdehyde content in egg yolks were also evaluated to determine the dietary quality of the eggs. The inclusion of HIM at any level in the diet did not affect the laying performance parameters (p > 0.05). Increased serum Ca and uric acid contents were observed. There was no effect on the redox indices in plasma. The number of hepatocytes was decreased in the HIM-fed groups. The level of cholesterol in yolks was reduced, and the fatty acid profile showed significant changes. Despite the high lauric acid content in the H. illucens meal, it was present in trace amounts in yolks. In the HIM-fed groups, the levels of saturated fatty acids increased significantly, whereas those of unsaturated fatty acids decreased in the yolks in the same groups.This study was carried out on 96 caged Bovans Brown laying hens at an initial age of 25 weeks, which were randomly assigned to four experimental groups of 12 replicates (cages) of two hens per cage. The control group hens received a diet containing 20% soybean meal (SBM), without  According to the United Nations, egg production will increase to 89 million tons by 2030 , which wFollowing the European Union Commission Regulation 2017/893 of 24 May 2017, insects of some species, which are bred for the production of processed animal protein derived from insects, gained the status of “farmed animals”. Initially, the use of processed animal protein of insects was only possible in aquaculture and fur animals; however, the European Commission Regulation 2021/1372 of 17 August 2021 extended the scope of the target animals to include poultry and pigs.Hermetia illucens) seems to be a promising species that can effectively convert organic matter from waste into insect biomass with a high protein and fat content, which can be further used in poultry nutrition [H. illucens larvae from which the meal is produced have sufficient levels of lysine, methionine, threonine, isoleucine, and valine to meet the nutritional needs of poultry [H. illucens as feed also contain antimicrobial peptides (AMPs), produced by their immune system, thus enabling them to thrive under harsh environmental conditions [Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus subtilis [H. illucens larvae may have a negative impact on the health of laying hens or the nutritional value of eggs because they are rich in lipids, with saturated fatty acids (SFA) being predominant, especially medium-chain lauric, myristic, and palmitic acids [H. illucens meal (HIM) have shown that the complete substitution of SBM in hen diet may lead to reduced laying performance as evidenced by reduced feed intake and a decrease in average egg weight [Black Soldier Fly . The water and feed in mashed form were offered to all birds ad libitum. The birds were randomly divided into four groups, each containing an equal number of 12 replicate cages with two hens per cage. The hens from the control group received a feed mixture containing 20% of postextraction SBM, with no HIM content (HIM 0%). The birds in the experimental groups received a diet containing defatted H. illucens meal at a level of 5, 10, and 15%  at the expense of a proportionally decreasing content of postextraction SBM. All diets met the nutritional requirements for laying hens following Polish recommendations [H. illucens meal and SBM used in the experiment are presented in For this experiment, 96 17-week-old Bovans Brown laying hens were purchased from a commercial source and kept in enriched cages on a wire-mesh floor. Two birds were placed in each cage measuring 30 cm × 120 cm × 50 cm, corresponding to 3600 cmDuring the 12-week experiment, feed intake, the number of eggs, and their weight were recorded, and the laying performance, the egg weight, the daily mass of eggs per hen, daily feed intake, and feed conversion per egg and per 1 kg of eggs were determined.Two eggs from each cage were collected at the end of the 36th week of age. Yolks were separated and frozen at −20 °C until the FA composition and the cholesterol content of the yolks were determined. Additionally, during this period, two additional eggs from each cage were collected and stored for 14 days in a refrigerator (c.a. 5 °C); then, the yolks were separated, frozen, and lyophilized to determine the malondialdehyde content (MDA) using the thiobarbituric acid (TBA) method.g for 10 min to obtain serum for further analysis of biochemical and oxidative status indices. Heart, gizzard, liver, pancreas, spleen, and abdominal fat samples were separated and weighed to determine their relative weight to live body weight. Liver samples were collected for histological examination, and the rest of the tissue was frozen for further analysis of the fat and MDA contents.At the end of the experimental period, one hen from each replicate cage was randomly selected, weighed, and slaughtered by cervical dislocation after electrical stunning. Immediately after slaughter, blood was collected in tubes without an anticoagulant. The blood samples were then centrifuged at 3000× In accordance with the guidelines of Commission Regulation (EC) No. 152/2009 of 27.01.2009, the dry matter (Annex III A), crude protein (Annex III C), crude ash (Annex III M), crude fat (Annex III H), crude fiber (Annex III I), and amino acid (Annex III F) contents, excluding tryptophan, were determined for the experimental diets, HIM and SBM. The tryptophan content was determined after alkaline hydrolysis according to procedure SOP M.006 issue 6 of 27 January 2020. Micronutrients and macronutrients in the feed materials and experimental diets were determined using flame atomic absorption according to SOP M.010 issue 4 of 24 February 2020, for copper, manganese, iron, and zinc and SOP M.008 issue 5 of ’24 February 2020, for calcium, magnesium, sodium, and potassium. The FA contents in HIM and SBM, as well as in the egg yolks, were determined using gas chromatography according to procedure P 015 issue 2 of 1 March 2016. The cholesterol content in the egg yolks was determined using the gas chromatography method according to SOP M.023 issue 2 of 27 January 2020. The MDA levels in the egg yolks and liver samples were determined using the TBA method according to Pikul et al. [The following biochemical indices were determined in the blood serum samples using commercial kits : Tp; albumin; triglycerides (TG); total cholesterol (TC); high-density lipoprotein; low-density lipoprotein; uric acid (UA); Ca, P, Mg, and Fe concentrations; and enzyme activities of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, amylase, and lipase.The serum levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and MDA were measured using commercially available ELISA kits from the Bioassay Technology Laboratory , according to the manufacturer’s instructions.2 of the cross-sectional area of the liver samples was counted. For each hen, two slides with five regions of interest (ROI) per slide were analyzed, and the hepatocytes present in each ROI were counted using a Cell counter plugin for ImageJ software. The average number of hepatocytes from all ROI per unit area was then calculated. The hepatic steatosis level was scored according to the 3-point scale  for 24 h, dehydrated in a graded series of ethanol, cleared with a nonpolar solvent, and then embedded in paraffin . Then, 4-µm-thick cross-sections were cut using a microtome  and then placed on a microscopic slide . The slides were stained with Harris hematoxylin and alcoholic eosin Y . The level of fibrosis was assessed using the Masson Goldner Trichrome Staining Kit . The stained slides were observed using a light microscope  that was equipped with an Axiocam Color 105 camera  using the graphical analysis software ZEN 2.3 blue edition software version 2.3  and ImageJ version 1.53 . The number of hepatocytes per 0.1 mmnt scale :1—No steatosis or single lipid droplets in the cells;2—Visible lipid droplets in a large part of the cells (about 30–45%), morphologically altered cells;3—Extensive steatosis, more than 50% of cells contain lipid droplets and/or fat vacuoles, cells morphologically altered, visible changes in the cytoplasm of cells, and nuclei often arranged peripherally.p ≤ 0.05 were considered significant.The data were analyzed using STATISTICA, version 13.3 . For statistical analyses, each replicate cage was treated as an experimental unit. The Shapiro–Wilk test for normality of the data distribution and Levene’s test for homogeneity of variance were used. For normality and variance homogeneity, one-way ANOVA was carried out, followed by Duncan’s multiple-range post hoc test. For nonnormally distributed data, the Kruskal–Wallis test was carried out. When significant differences were detected using the Kruskal–Wallis test, a post hoc test for pairwise multiple comparisons of the ranked data was used. Values of p > 0.05). The mean laying rate, averaged across all dietary treatments throughout the entire experimental period (25–36 weeks of age), was 98.0%; daily egg mass, 57.7 g/hen; egg weight, 58.9 g; daily feed consumption, 120 g/hen; and feed conversion, 122.4 g of feed/egg or 2.08 g of feed/g of eggs.The laying performance of the hens is presented in p > 0.05) in the relative weights of the gizzard, heart, liver, spleen, and pancreas, as well as in the relative abdominal fat weight .Serum redox indices are presented in p > 0.05). However, it increased the fat content, and the values for the HIM 5%, HIM 10%, and HIM 15% groups were 8.3, 9.4, and 7.7%, respectively, higher than that of the control group.The HIM administration in the diets of laying hens did not significantly affect the liver MDA and liver fat contents, as shown in p > 0.05). Moreover, the liver tissue in all experimental groups was free of pathologic fibrosis. However, the number of hepatocytes significantly decreased in the HIM 10% and HIM 15% groups, compared with the control group. In some hens with high levels of steatosis cells (scored at three points), irregular structure and distribution of hepatocytes were observed. Furthermore, balloon cells near lipid droplets were also observed in these birds.As presented in p = 0.020). In eggs collected at 36 weeks of age and refrigerated for 14 days, the MDA content of the yolks of all HIM groups was comparable to that of the control group; however, the MDA content of the yolks was significantly higher in the HIM 10% group than in the HIM 5% group.The results of the analysis of cholesterol level, FA profile, and MDA content in the egg yolks are summarized in In egg yolks, the lauric acid, myristic acid, and SFA contents were significantly increased in the HIM 10% and HIM 15% groups, proportionally to the increasing HIM content in the diet, compared with the values observed in the control group; however, the arachidic acid, docosahexaenoic acid, unsaturated fatty acids (UFA), polyunsaturated fatty acids (PUFA) n-3, and UFA/SFA contents were decreased. The total monosaturated fatty acids content was not affected. The linoleic acid and gamma-linolenic acid contents were decreased in the HIM 10% group, and the linolenic acid, total PUFA, and PUFA-6 contents were significantly decreased in the HIM 5% and HIM 10% groups than in the control group. As a consequence, with the increase in the content of HIM in the diet, the content of desirable fatty acids significantly decreased, whereas the PUFA 6/3 content significantly increased in the HIM 15% group, compared with the control group.in vitro [In the present study, the partial replacement of SBM with defatted HIM up to the level of 15% in the diet of laying hens was not found to affect the laying rate. Similar results were reported in a study by Mwaniki et al. , where 1in vitro . Furtherin vitro . Moreovein vitro  or broilin vitro  fed HIM In the present study, the HIM diets did not significantly affect the relative weights of organs, whereas an increase in the relative weights of abdominal fat was observed. Mwaniki et al.  reportedThe experimental diets were calculated to provide an equal level of Ca; however, the analyzed content of Ca was 43.6, 43.1, 45.4, and 40.7 g/kg in the HIM 0%, HIM 5%, HIM 10%, and HIM 15% groups, respectively. Despite the lower Ca content of the HIM 15% diet, plasma calcium levels increased significantly in all groups of HIM-fed hens. This may be due to the prebiotic properties of chitin contained in the insect’s exoskeleton. By modulating the intestinal microflora, it leads to increased production of short-chain fatty acids (SCFAs) , increasIn the present study, significant increases in the serum uric acid level were observed in the HIM 5% and HIM 10% groups. The higher UA content may be due to the difference in amino acid utilization . NeverthTenebrio molitor meal as a total replacement for SBM in the diet, also observed no significant differences. However, Morono et al. [Similar to the present results of unaffected serum TG and TC levels, Bovera et al. , using ao et al.  reportedo et al. .High animal productivity is often accompanied by oxidative stress, which indicates a reduction in the antioxidant capacity , i.e., dH. illucens, indicating that the insect meal was its major source in the experimental diets. With the increase in the level of HIM in the diet, the C12 content in the yolk increased, but despite a significant increase (p < 0.001), the analyzed content remained at a lower level, ranging from 0.0267 to 0.08 g per 100 g of the total FA content. Similar results were obtained by Heuel et al. [While considering the dietary quality of eggs, emphasis is placed on the lipids in the yolk, which constitute 65% of the dry matter of the yolk . Signifil et al.  showed nl et al. . The degThe inclusion of HIM in the diet for 12 weeks did not worsen the laying performance or affect the function of the liver and pancreas. HIM did not significantly alter most of the serum biochemical indices but increased the serum Ca content. Thus, it may be regarded as an efficient alternative protein source for laying hens. However, it negatively altered the liver histology and unfavorably changed the yolk FA profile, which needs further investigation.


The creation of novel anticancer treatments for a variety of human illnesses, including different malignancies and dangerous microbes, also potentially depends on nanoparticles including silver. Recently, it has been successful to biologically synthesize metal nanoparticles using plant extracts. The natural flavonoid 3,3′, 4′, 5,5′, and 7 hexahydroxyflavon (myricetin) has anticancer properties. There is not much known about the regulatory effects of myricetin on the possible cell fate-determination mechanisms (such as apoptosis/proliferation) in colorectal cancer. Because the majority of investigations related to the anticancer activity of myricetin have dominantly focused on the enhancement of tumor cell uncontrolled growth . Thus, we have decided to explore the potential myricetin interactors and the associated biological functions by using an in-silico approach. Then, we focused on the main goal of the work which involved the synthesis of silver nanoparticles and the labeling of myricetin with it. The synthesized silver nanoparticles were examined using UV-visible spectroscopy, dynamic light scattering spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy. In this study, we have investigated the effects of myricetin on colorectal cancer where numerous techniques were used to show myricetin’s effect on colon cancer cells. Transmission Electron Microscopy was employed to monitor morphological changes. Furthermore, we have combined the results of the colorectal cancer gene expression dataset with those of the myricetin interactors and pathways. Based on the results, we conclude that myricetin is able to efficiently kill human colorectal cancer cell lines. Since, it shares important biological roles and possible route components and this myricetin may be a promising herbal treatment for colorectal cancer as per an in-silico analysis of the TCGA dataset. A quick, suitable, and acceptable biosynthetic method is the phyto-mediated synthesis for the production of metal nanoparticles (NPs) ,2,3,4. INumerous physical and chemical techniques, including a reduction in solutions, chemical and photochemical reactions in reverse micelles, thermal decomposition of silver compounds, radiation-assisted, electrochemical, sonochemical, microwave-assisted processes, and, most recently, green chemistry technology, have been used for the synthesis of AgNPs. In terms of cost-effectiveness, environmental friendliness, and simplicity of scaling up for large-scale synthesis without the use of energy, high pressure, temperature, or toxic chemicals, the green synthesis approach exceeds the chemical and physical methods ,9,13.Studies on the creation of AgNPs from various plant sources have been reported in previous works. There is still a need for an environmentally pure, economically sound, and commercially viable method to synthesize AgNPs despite the use of new plant sources. In recent years, there has been a lot of interest in the use of plants and plant-based products in the production of different metal nanoparticles ,9,10,14.For patients with a range of cancer types, such as melanoma, breast, and lung cancers, biomarker-driven customized therapy has made impressive progress toward precision oncology also for patients with colorectal cancer (CRC) ,24,25,26Cancer develops and spreads as a result of the accumulation of biological traits that may help tumor cells thrive, proliferate, escape immune monitoring, and become more resilient under challenging circumstances. The creation of tumor molecular maps has aided in the development of novel inhibitors that specifically target the altered genes and signaling pathways driving the malignant phenotype ,42,43,44The second deadliest and third most common disease in the world and based on the available reports, CRC is known to cause more than 1.7 million new cases and approximately 862,000 deaths in 2018 . TreatmeNumerous foods, such as fruits, herbs, and nuts, contain a pigment known as myricetin , which is a kind of flavonoid. The 3′,4′,5′-trihydroxy group on myricetin makes it unique from the other flavonols. It has been demonstrated that myricetin has anticancer properties in a number of cancers, including prostate, breast, stomach, and CRCs ,18,20,52Because conventional cancer medicines have intrinsic limits, many nanotechnologies have been developed and put to use to treat cancer more effectively and safely, a field known as cancer nanomedicine. Although there has been significant technological advancement in this area, the complexity and heterogeneity of tumor biology, a lack of knowledge of nano-bio interactions, and the difficulties in chemistry, manufacturing, and control that must be overcome for clinical translation and commercialization are the main obstacles to nanomedicine becoming a new paradigm in cancer therapy. Here, we have used a novel strategy to demonstrate the increased efficacy of nano-therapeutics against cancer patients by utilizing our knowledge of antitumor and nano-bio interactions. The summarized steps have been presented in As mentioned in the previous section the significance of myricetin and its potential role in cancer mainly CRC, thus we proceeded to our next goal where we wanted to label this herbal drug with AgNPs so we proceeded towards the synthesis and characterization as an initial step. The UV-vis spectra has been used for the investigation of proper embedding/labeling of myricetin with AgNPs and the UV-vis spectra of myricetin extract and the AgNPs were displayed in The presence of nanoparticles was confirmed by obtaining a spectrum in the visible range of 300 nm to 500 nm using a UV-visible spectrophotometer . From th3) was prepared in 250 mL conical flasks, and myricetin (1 mM) was added for reduction into Ag+ ions. The mixture was then stirred overnight. By using UV-vis spectrophotometric analysis, the color shift of myricetin from light yellowish to reddish brown was noted. The identical combination was made and aged for 24 h prior to being observed using UV-vis spectrophotometry as a comparison. The solution was filtered to produce tiny particles so that they could be thinly coated on the glass surface for XRD and SEM investigation. AgNPs-mw and AgNPs-aging are the names given to the AgNPs produced by microwave irradiation and aging processes, respectively. The volume ratio in the AgNPs-mw preparation was adjusted at a 10:1 ratio in order to assess the impact of the silver nitrate solution’s volume ratio relative to the myricetin on the particle size distribution and its antibacterial activity.Aqueous solution (1 mM) of silver nitrate (AgNOThe microstructure of the BioAgNPs or mAgNPs (myricetin silver nano-particles) synthesized and was analyzed by scanning electron microscopy (SEM). The produced AgNPs are in the 12–20 nm nanoparticle size range, according to TEM profiles in With the use of Shimadzu X-6000  equipment and Rietica, the Rietveld refinement of AgNPs was carried out. Before analysis, the powdered AgNPs were spread over a glass film after the sample’s solvent had evaporated d.XRD is an analytical technique used to identify the phase of a crystalline substance and to study the structure of crystals. In this technique, X-rays are produced in a cathode ray tube and get filtered to form monochromatic radiation that interacts with the sample and forms constructive interference. AgNPs synthesized using the Myricetin confirm the XRD pattern, as shown in y 61 nm) e.The distribution implies that during the fast reduction process brought on by microwave irradiation, particle aggregates are formed with increased energy transfer. The shift in the volume ratio suggests that the particle size diameter distribution of the AgNPs will be smaller the greater the concentration of Myricetin extract. The means of the particle size distribution are displayed in −1, and some other peaks approximately at 1000 cm−1. The peak at 3292 cm−1 represents the AOH stretching vibration from phenolic compounds in the extract while the three peaks at 2849, 1375, and 1043 cm−1 are probably attributable to the NH stretching vibration of amide II, CAO stretch, and CAN stretching of amines, respectively. The peak at 1630 cm−1 is designated as the stretching vibration of the C‚O bond. After the Ag NPs formation, there are some shifts of valuable peaks such as the O-H vibration from 3292 to 3306 cm−1, C‚O vibration from 1630 to 1634 cm−1, and NAH vibration from 1043 to 1045 cm−1, indicating that reduction occurred. Overall, the spectra of AgNPs-mw and Ag NPs-aging are similar. FTIR data suggest that its functional group (-COOH) has been identified.A comparison of the FTIR spectra of the BP extract and AgNPs is displayed in Using cell viability assay, we evaluated the effects of AgNPs, pure myricetin, and myricetin labeled with AgNPs (mAgNPs) in normal cell line i.e., control (HEK-293) a and in Finally, we have selected the CRC dataset (GSE44076) with gene expression and performed gene expression and pathway enrichment analysis. The selected dataset contains the healthy, adjacent, and primary adenocarcinoma samples, so we have compared healthy with adjacent samples, healthy with primary adenocarcinoma, and adjacent with primary adenocarcinoma samples and thus generating three differentially expressed genes (DEGs) list a. FurtheIn pathway enrichment analysis, we observe that there were only three pathways that were common to all , 50 common between healthy versus primary adenocarcinoma cells DEGs list and adjacent cells versus primary adenocarcinoma cells DEGs list, no pathway was common between Healthy versus primary adenocarcinoma cells DEGs list and healthy versus adjacent cells DEGs list, and no pathway was common between healthy versus adjacent cells DEGs list and adjacent cells versus primary adenocarcinoma cells DEGs list . While 2Ampelopsis sinica (Miq.) W.T. Wang and Camellia sinensis (L.) Kuntze and the bark of Myrica nagi Thunb [Chinese herbal therapy has been found to enhance immune function, encourage reticuloendothelial system phagocytosis, safeguard the bone marrow’s ability to produce blood cells, and prevent drops in platelets and white blood cells. Traditional Chinese herbal remedies have become more and more popular in recent years for the adjuvant treatment of cancer ,54,55,56gi Thunb ,22,57. Tgi Thunb ,53,58,59A crucial intracellular signaling mechanism for controlling the cell cycle is the PI3K/AKT/mTOR pathway. As a result, it has a direct bearing on cellular dormancy, proliferation, cancer, and aging. According to Phillips PA, myricetin triggered apoptosis and inhibited the PI3K signaling pathway, which led to the death of pancreatic cancer cells. The PI3K/AKT/mTOR signaling pathway may control autophagy and have an impact on cellular growth. Western blotting was performed in our work to identify the various signaling pathways in myricetin-treated HCT116 and SW620 cells, and the results showed that the PI3K/AKT/mTOR signaling pathway was responsible for inducing cell death and autophagy.The inhibitory effects of myricetin on colon cancer entail both apoptosis and autophagy, two different types of cell death. Previous studies have discovered that the processes of autophagy and apoptosis take place in the same cells ,36. AccoWe have directly collected the herbal drug myricetin (M670-25MG) from Sigma-Aldrich which has CAS 529-44-2.3 solution; the AgNO3 was purchased from MERCK. As a control, however, the identical experimental setup with 1 mL of myricetin and 9 mL of distilled water was maintained. Both flasks were incubated at 25 °C in the dark for 2–4 h using a rotary shaker. Later, the generated AgNPs were separated and purified by continuous centrifugation in sterile miliQ water at 10,000 rpm for 20 min at 4 °C. In order to further characterize and examine the bioactivity of the dried AgNPs, they were stored at 4 °C [The appropriate reaction mixture for the biogenesis of silver nanoparticles was created by mixing 1 mL of myricetin with 9 mL of 1 mM AgNO at 4 °C ,8.+ ions) in an aqueous solution was monitored periodically in a UV-Vis spectrophotometer (Hitachi U3900) within the range of 200–600 nm. The UV-visible spectra of the resulting reaction solution were monitored as a function of reaction time at a resolution of 1nm room temperature (25 °C). The purified samples were 10-folds diluted with the phosphate buffer saline PBS . The aliquots were later sampled in dynamic light scattering (DLS) cuvettes and examined for equivalent diameters, size distribution, and zeta potential. The particle diameters were assessed at a scattering angle of 90° at room temperature (25 °C). Fourier Transform Infra-Red spectra of the AgNPs were studied in an FT-IR spectrophotometer (Bruker Tensor 37) in transmission (%) mode with 200 scans. The AgNPs were pelletized with potassium bromide (KBr) having a 1% sample concentration (w/w) and were analyzed against the background of a pure KBr pellet. The nano-scale size of silver particles was confirmed by the analysis of morphological structure under a scanning electron microscope  performed at an acceleration voltage of 15 KV [The biosynthesis of the AgNPs  at 37 °C in a 5% COironment ,62,63.The MTT cell viability test was used to gauge cell viability. In 96-well culture plates, the cells were planted at a density of 1 × 104 cells/well. Different myricetin concentrations  were added after 4 h, and the mixture was then incubated for 24 h. As a control, cells were treated in culture media containing a similar volume of dimethyl sulfoxide (DMSO). To calculate the cell survival rate, the absorbance was measured using a microplate reader at 570 nm excitation/emission wavelengths ,65.4 for 1 h, the cells were first fixed for 2 h with 2.5 percent glutaraldehyde and 2.5 percent formaldehyde. The cells were then treated progressively with acetone/resin Spur’s , ethanol, and 100 percent Spur’s resin after being soaked in 2 percent uranyl acetate for 1 h. The ultrathin cell sections were seen using transmission electron microscopy [With the help of traditional electron microscopy, cell size was determined. Prior to being treated with 1 percent OsOcroscopy ,66.t-test statistical analysis was conducted using SPSS/Win 13.0 program for pair samples. The findings are shown as the mean ± SD, and significant findings are denoted by the following symbols: * p = 0.05, ** p = 0.01 and *** p = 0.001.In this study, we proposed to investigate the genes and signaling pathways that are active in lung cancer patients, as well as to find potential targets and herbal remedies that might interfere with these processes ,68,69,70https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE44076) dataset contains healthy, adjacent, and adenocarcinoma samples and processed it until normalization and log2 values of all the mapped out the genes as mentioned.In the first step, we have selected the data of our interest (raw expression datasets) GSE44076 (We have compared the samples (control) to the corresponding samples (target/CRC) for differential gene expression analysis, yielding DEGs lists. Raw file processing, intensity computation, and normalization are the basic procedures involved in the entire study. GCRMA, RMA, and EB are the most often used techniques for normalization. For raw intensity normalization, EB was utilized for raw intensity normalization. Following normalization, we moved toward the main goal of understanding gene expression patterns ,67 and tIn order to generate DEGs lists, we compared three distinct types of samples to their corresponding samples for differential gene expression analysis. The three main processes that are used during the whole study are raw file processing, intensity computation, and normalization. The three methods for normalizing that are most frequently used are GCRMA, RMA, and EB ,74,75,76t-test to analyze the differential expression of genes from two experimental circumstances or phenotypes. MATLAB tools, such as mattest, have been utilized for differential gene expression prediction and statistical analysis. In this situation, a matrix of gene expression levels is required, with each row denoting a gene and each column denoting a replication. Target and normal data both need to have the same number of rows and be normally distributed with comparable variations across classes. We have used the KEGG [The mattes MATLAB function runs a two-sample the KEGG  databasethe KEGG ,87,88,89the KEGG  was usedthe KEGG  was usedNumerous malignancies have shown myricetin to have anticancer effects. The precise processes behind these impacts are not entirely understood, yet. There is limited research on myricetin’s effectiveness as a colon cancer anticancer agent. Based on our results we conclude that, myricetin drastically reduced the growth of HCT116 cells in a dose-dependent way and after 100 µg/mL, the cytotoxicity appears to be stable. Furthermore, myricetin interactors and pathways are also shared with CRC via critical biological functions and its components. This result suggests that myricetin could be the potential herbal drug to target the CRC pathways and pathway components. This study could add to the body of data supporting the use of myricetin as a colon cancer therapy. The findings form the basis for creating natural product-based anti-colon cancer medications that are more effective. Future studies are required to provide highly efficient antitumor medications that specifically target cancer cells.


Histiocytic sarcoma (HS) is a rare neoplasm composed of cells with immunohistochemical characteristics of mature histiocytes. It can be disseminated or localized and usually involves the skin, spleen, and gastrointestinal tract. Primary involvement of the vertebral column is extremely rare. We report a 29-year-old female who presented with neck pain and had a destructive 35*43*48 mm lesion in C2 with a paravertebral extension. The initial biopsy did not lead to the correct diagnosis. She later developed dysphagia, and the anterior approach was used for tumor decompression. The diagnosis of cervical histiocytic sarcoma was made, and she underwent radiotherapy. The follow-up MRI showed a marked response to radiotherapy. Here, we report the first case of cervical HS, review all cases of vertebral HS, compare patients’ characteristics and clinical courses, and discuss diagnostic nuances and treatment options. Histiocytic sarcoma (HS) is a malignant proliferation of cells showing the morphological and immunophenotypic characteristics of mature histiocytes. Histiocytes are phagocytic, antigen-presenting cells that originate from hematopoietic stem cells that perform the processing and destruction of antigens. Derived from these cells, HS is an aggressive neoplasm with poor outcomes. It can be disseminated or localized in the skin, lymph nodes, gastrointestinal tract, or other organs. HS was not a known lesion until the development of immunohistochemistry and the availability of molecular genetic tools, and most cases were previously diagnosed as lymphomas such as diffuse large B-cell lymphoma (DLBCL) or anaplastic large cell lymphoma (ALCL) ,2. The dPrimary HS in the spine is extremely rare and has been reported in only six cases ,6,7,8,9.The patient was a 29-year-old female with an initial complaint of neck pain and limited mobility. In a cervical CT scan, the complete destruction of the second cervical vertebra was obvious. In the MRI of the cervical spine, a large heterogenous tumoral mass in the C2 vertebra with some necrotic/cystic parts and a marked paravertebral extension was seen. It was almost isointense to the cord in the T1W and T2W images and was heterogeneously enhanced with gadolinium . The thoBecause of vertebral instability, the patients underwent craniocervical fixation and tumor sampling through the C2 pedicle. The histopathologic examination reported an atypical histiocytic tumor infiltrated with hemophagocytosis. In the immunohistochemical examination, CD3, CD15, CD20, CD30, CD34, S100, GFAP, desmin, and EMA were negative and CD68, CD163, and vimentin were positive. ki67 was 15%. The positron emission tomography (PET) scan showed two FDG avid skeletal lesions, one in the C2 odontoid process (SUV max = 7.8) most consistent with Langerhans cell histiocytosis and the other one in the right iliac bone (SUV max = 4.5) consistent with the place of the bone graft extraction at surgery.Three months later, the patient’s symptoms worsened, and she developed dysphagia. A repeat MRI showed a significant increase in the size of the tumor and a paravertebral extension (35 × 43 × 48 versus 52 × 42 × 60) . This tiAt the end of the radiotherapy period, the patient suffered from a sudden monoparesis of the left upper limb. The CT scan indicated a hypodense lesion in the head of the caudate nucleus, putamen, and anterior thalamus, which was hyperintense in the T1- and T2-weighted MRI. In the MRA, the right internal carotid artery was not visible . The patSix months after radiotherapy, the MRI showed a very good response to the treatment, with no mass lesion and non-specific enhancement at C2 and C3 . The thoHS is a very rare neoplasm of the hematopoietic system that usually presents in extranodal sites as a painless mass. Common locations are the gastrointestinal tract, skin, spleen, and liver. The median age at diagnosis is 51, and it predominates in males . It invoThe diagnosis of HS is based on histologic appearance and, more importantly, immunohistochemical tests. Langerhans cell sarcoma (LCS), peripheral T-cell lymphoma, diffuse large B-cell lymphoma, anaplastic large cell lymphoma (ALCL), and melanoma can make diagnosis a challenge. CD163 is very useful, is specific for HC, and was the only factor in Pileri’s series that was positive in all cases of HS . ImmunohExcept for two cases reported in 3- and 63-year-old patients, most cases of vertebral HS had involved young adults between 17 to 29 years old . TreatmePileri et al. published a series of patients with histiocytic tumors and reported the first available case of primary vertebral involvement, a 26-year-old male who presented with lytic lesions at the T4 and T5 vertebra. He was previously treated for L2 leukemia . Lin et Buonocore et al. reported a 3-year-old boy who presented with low back pain. There were complete T6 and L4 collapses, with an epidural mass at L4. There was no other involved focus. They started chemotherapy  and radiotherapy (4500 cGy in 180-cGy fractions) to the L4 vertebra, which led to size reduction at the L4 epidural space. He then developed two pulmonary nodules which were managed again by chemotherapy  and radiotherapy (4500 cGy at 180 cGy per fraction). They found a poor response to LCH- and sarcoma-based chemotherapy and a slightly better response to idarubicin and 2CdA. They have noted that the clinical improvement was seen after the second half of the radiotherapy course, and, interestingly, the T6 lesion did not progress despite no radiotherapy at this level .Getting all these reports together , it is cThere is no standard treatment for HS, but the most used treatments are a combination of surgery, radiotherapy, and chemotherapy. The optimal dose of radiotherapy and the chemotherapy regime is also unknown ,16. In tHS is a very aggressive tumor with a poor prognosis. According to a study by the National Cancer Database (NCDB) on 330 cases of HS, after a median follow-up of 16 months, 227 patients (69%) had died. The median OS was 6  months [Recent advances in developing target therapies have shown some promise in the treatment of HS. Because of the involvement of the MAPK/ERK pathway, different molecules in this pathway, such as BRAF, MAPK, KRAS, and MEK, may be potential targets for the modification of the pathology. The MEK inhibitor trametinib and the BRAF inhibitor vemurafenib have been tried for histiocytic tumors, with acceptable responses in some cases .Primary HS of the spinal column is extremely rare. One should have a strong suspicion and perform extensive IHC tests to detect the pathology. The treatment options are not standard, but most authors insist on surgery plus chemotherapy and radiotherapy. Although the surgical procedure attempted just a tumor debulking, this patient showed a very good radiologic response to radiotherapy. So, we showed that when a total resection of the tumor is not possible, radiotherapy with 4500 cGy in 25 fractions for the isolated primary HS of vertebral bodies is a viable option. Moreover, target therapies, particularly addressing the MAPK pathway, may change the future of the treatment for HS cases.


Puccinia triticina E. The accessions were screened against two races CBG/BP and BBG/BP in the field at two locations: against race CBG/BP at the Norman E. Borlaug Experimental Station (CENEB) located in the Yaqui Valley in the northern state of Sonora in Mexico during the 2014–2015 growing season; and against race BBG/BP at CIMMYT headquarters in El Batan, Texcoco, in the state of Mexico in the summer of 2015. Among the accessions, 79 durum genotypes were identified, of which 68 continued demonstrating their resistance in the field (past the seedling stage) against the two leaf rust races. An additional set of 41 genotypes was susceptible at the seedling stage, but adult plant race-specific resistance was identified in the field. The 79 seedling-resistant genotypes were tested against 15 different leaf rust races at the seedling stage to measure the usefulness of their resistance in a breeding program. Among the 79 accessions tested, 35 were resistant to all races used in the tests. Two sample sources, CIMMYT (18/35) pre-breeding germplasm and Ethiopian landraces (17/35), showed seedling resistance to all races tested except for seven landraces from Ethiopia, which became susceptible to the Cirno race identified in 2017. A collection of 482 tetraploid wheat accessions from the CIMMYT Germplasm Bank was screened in the greenhouse for resistance to leaf rust disease caused by the fungus  Triticum turgidum var. durum) is grown on about 13 million hectares worldwide, half of which are found in developing countries. Most durum varieties under cultivation in developing countries are either derived from germplasm improvement programs at the International Maize and Wheat and Improvement Center (CIMMYT) or the International Center for Agricultural Research in the Dry Areas (ICARDA). Durum wheat is host to two species of fungi that cause leaf rust: (1) Puccinia triticina E., which is the most common and widely distributed [P. tritici-duri V.-Bourgin [P. triticina races virulent on durum wheat (T. turgidum) are different from those that are virulent on bread wheat (T. aestivum). The durum P. triticina races are avirulent to the majority of the known leaf rust host differentials, carrying resistance genes that are commonly present in bread wheat cultivars; therefore, their survival, selection, and spread are usually restricted to durum growing areas. During the last two decades, new durum leaf rust races with specific virulence have rendered many cultivars susceptible in several countries. In Mexico for example, during the 2001 growing cycle, race BBG/BN [Lr72 [Lr14a identified in Mexico. The economic losses in Mexico to durum wheat producers because of epidemics from 2001 to 2003 caused by the Altar C84 virulent race BBG/BN were estimated to be over USD 32 million [Lr27+31 present in cultivar Jupare and Banamichi, and CBG/BP with additional virulence for Lr3 defeated the genotype Storlom [Spring durum wheat . Among the durum cultivars evaluated, 258 accessions were seedling susceptible to both races and displayed different degrees of slow rusting type of resistance at the adult stage (data not shown), and 114 seedling resistance were considered as susceptible to both races (data not shown). Therefore, no agronomic value from the disease resistance point of view at this time was considered.The seedling-susceptible accessions that displayed compatible infection type at the adult stage are not reported in the present study as a different approach to describe them is needed. When grouping the seedling-resistant and seedling-susceptible adult plant-resistant accessions by their origin, they represented 24 countries, the CIMMYT pre-breeding program, and other unknown or non-specified origins. Out of 110 entries, 69 were resistant from seedling to the adult stage , and 41 Lr11, and Lr18 [Lr13, could be more effective at higher temperatures [Between the two locations used for the adult plant testing, the conditions for rust development at El Batan are more favorable since the growing cycle coincides with the rainy season where more daily moisture is available, and days with prolonged dew formation favor successive reinfections by the fungus. However, in some entries, the level of the disease was higher at the CENEB location since some resistance genes are more effective at lower temperatures, such as and Lr18 , whereaseratures .Lr72 present in Altar C84 and Atil C2001 cultivars. Seedling resistance to all races tested could be the most valuable resistance identified for the short term in a breeding program for countries where both durum and bread wheat are cultivated in the same areas. Several accessions identified as seedling resistant to both durum leaf rust races BBG/BP and CBG/BP were seedling susceptible to at least one race that prefers to attack bread wheat. These genotypes represent a valuable source of resistance against durum leaf rust races, but in this case, resistances identified must be used in combination with other effective sources against all races coming from bread wheat such as P. triticina races coming from bread wheat isolates [P. triticina races used in these studies will determine the sources of resistance identified, keeping in mind that in some instances, most durum accessions could be resistant to races collected from bread wheat, but the same accessions could be susceptible to races collected from durum wheat [Recent studies have clearly demonstrated the potential of landraces to contribute diverse alleles for economic traits ,35,36,37isolates . The P. um wheat . In otheum wheat , and durum wheat  and Martum wheat .Lr9 [Lr9 in these accessions was confirmed by inoculating them with a culture virulent to Lr9 and one avirulent to Lr9 (data not shown). Entry G5392 is a cross with RL6043/Nacozari, which could indicate the presence of Lr21 [Lr10 [Lr16, a leaf rust resistance gene identified in Olesen dwarf or from Santa Elena, both of which are parents of H567.71. Alternatively, Lr16 may descend from a durum parent since Zhang and Knott [Lr16 was identified in a Triticum carthlicum Blackbird cultivar through molecular markers [Lr16 as a race-specific gene, however, is limited since at the adult stage Lr16 behaves more like a slow-rusting resistance gene—at least against leaf rust races, which preferably attack bread wheat. In bread wheat cultivars, when Lr16 is alone, disease severity goes from 30MS to 60MS in response to isolates avirulent on seedling (IT 1 to 11+). This explains why, among the race-specific resistant seedlings, a few (11/79) were considered as susceptible at the adult stage. Other possible sources of resistance coming from bread wheat are entries G8743 from Sonora 64 (Lr1), and G5394 from Nacozari. The resistance in entries G5235, G5207, G5208, G5424, G3988, G6904, G5421, G8813, and G6857 might have come from the wild relatives T. diccocum, T. boeticum, T. monococum, T. carthlicum, T. rartu, T. polonicum, and Khapli-Emmer, respectively, as the durum parents involved in these crosses were susceptible. Among the wild emmer types of wheat, T. dicoccoides could be considered as the closest wild relative of the durum type [Among the seedling-resistant accessions identified in the present study, the majority are true landraces, and therefore, resistance could be considered as unique and different from what has been used in breeding programs already. In other instances, resistance can be traced back either to a bread wheat parent or to a close wild relative, particularly in genotypes from the CIMMYT pre-breeding program. For example, in the seedling resistance lines G5375 and G5369, the presence of RL6010 in the pedigree will allow us to postulate the presence of Lr9 . The pre of Lr21 . However21 [Lr10 . In the nd Knott  postulatrum type .Lr3, Lr10, Lr11, Lr12, Lr16, Lr23, Lr33, and Lr27+31, which are already common in bread wheat germplasm. In the case of G3988, G5424, and G5207, resistance is possibly coming from a wild relative. This resistance is effective against all leaf rust races tested at the seedling stage, which indicates that it might be very useful in the short term for breeding purposes if the aim is to incorporate race-specific resistance genes in breeding durum wheat for leaf rust resistance. The resistance identified in G8731, G3543, G67857, G6904, G5359, G5364, G5369, and G5394 possibly derives from a bread wheat source effective against all races tested in the seedling stage. However, these sources—although very useful—might be very similar if not the same as the resistance genes T. diccocum types. These sources of resistance may uniquely belong to the closest wild relative of the T. turgidum var. durum since they are still grown in farmers’ fields in Ethiopia; in fact, the dominance of violet, purple, or red grain color atypical to the more prevalent yellow color of improved germplasm confirms this assumption.Among the 17 lines from Ethiopia, which were resistant to all races tested at the seedling stage, except for CWI22214 and CWI20872, 15 lines appeared to belong to Among the seedling-susceptible adult-resistant plants, two growth habits could be identified: spring and/or winter photoperiod-sensitive types. In both groups, resistance varied from 0 to 40MR, similarly but with less frequency, and resistance coming from a bread wheat source or wild relative was identified. However, most of the resistant genotypes identified were true durum landraces. It is important to notice that, in many instances, lines could not be true landraces, but were introductions from centers of origin or centers of diversification, those whose origin is recorded as being from the Americas when early introductions occurred during the 15th century . Independent of the origin of durum wheat genotypes, the study reveals the existence of sources of race-specific resistance to leaf rust in the CIMMYT Germplasm Bank for both seedling resistant-adult resistant and seedling susceptible-adult resistant. In fact, these two sources can be combined to obtain higher levels of resistance and to assure not only diversity, but to increase the number of resistant factors in improved genotypes, which in time will confer higher and stable resistance across environments.However, the use of these sources of resistance to leaf rust in a durum wheat breeding program will require at least one backcross to an adapted genotype due to the variation in plant height. Most true landraces are typically tall (higher than 100 cm) except for those coming from pre-breeding programs, which are semi-dwarf (less than 100 cm). The second issue will be the red, violet, or purple seed coat color of the grain, and white to mild yellow endosperm. Although simply inherited, the preferred color for improved durum wheat is a very intense yellow pigmentation for not only the seed coat color, but also the endosperm color and its end-use quality of semolina and dry pasta .T. diccocum, and T. dicoccoides. The present subset could be used in an association mapping study to understand the degree of diversity among the resistant accessions against the durum leaf rust races in different countries and environments. Resistant landraces and pre-breeding genotypes identified in the present study will complement the efforts of searching for new sources of resistance and their use in breeding durum programs against leaf rust.This relatively small sample of the tetraploid collection from the CIMMYT Germplasm Bank represents a subset of the entire collection. However, the presence of high levels of resistance to wheat leaf rust suggests there is enough variation in the collection, and that in the short term, it is not necessary to look farther into the secondary gene pool for resistance other than into the tetraploid closest relatives such as Lr Camayo). This is evidenced by the following previously resistant lines becoming susceptible to the Cirno race: ABYSSINIAN 26 (CWI23065), ELS6404.131.3 (CWI23440), ELS6404.61.2 (CWI23473), HARLAN J.R 1939 (CWI21737), IAR.W.63.1 (CWI22175), IAR.W.84 (CWI22201), and IAR.W.92.1 (CWI22214). All these landraces were collected from Ethiopia. The defeated gene present in the Camayo parent of Cirno C2008 has an Ethiopian landrace origin—ETH-LRBR A1-133/3*ALTAR 84 [Lr72) was defeated in 2001 [The response of the resistant lines to the new race virulent on Cirno C2008  indicateAN 26 CWI065, ELS6Seedling resistance was determined by evaluating 482 durum wheat accessions from CIMMYT’s germplasm bank against two of the most recently identified leaf rust races, which have evolved in Mexico since 2001. These accessions comprised landraces and pre-breeding lines from 45 countries and included pre-breeding accessions coming from crosses made at CIMMYT. P. triticina races BBG/BP and CBG/BP [®  at a concentration of 5 mg/mL [For the greenhouse evaluation, 8 to 10 seeds of each line were sown in plastic trays filled with steam-sterilized soil. Plants were grown in a greenhouse at 18 to 22 °C with 16 h of supplemental light. Fourteen-day-old seedlings at the two-leaf stage were inoculated by spraying fresh urediniospores of d CBG/BP  suspende 5 mg/mL . After a 5 mg/mL . In thisLr3 based on the North American system of nomenclature [Lr1, 2a, 2b, 2c, 3bg, 3ka, 9, 13, 14a, 15, 16, 17a, 18, 19, 21, 24, 25, 26, 28, 29, 30, 32/Lr10, 12, 14b, 17b, 20, 23, 27+31, and Lr33 [The differences between CBG/BP and BBG/BP are found only in nclature  and addinclature . Their iLr61, which is avirulent to cultivar Altar C84 (Lr72), but virulent to Lr28, Gaza, and Lr61. Besides the durum leaf rust races CBG/BP, BBG/BP, BBB/BN-Lr61, an additional 12 different rust races isolated from bread wheat—CBJ/QB, CBJ/QL, CBJ/QQ, MCJ/SP, MCJ/QM, MCD/SN, MBJ/SP, NCJ/BN, MFB/SP, MBB/QN, MBB/BN, and TCB/TD—were included in the test, following the same procedure described above and used in the seedling test against races BBG/BP and CBG/BP.Seedling-resistant genotypes against BBG/BP or CBG/BP races were further evaluated against an additional race from durum wheat: BBB/BN-Lr3 carrier) were planted on each side of the experimental plots and as hills in the alleys between plots to assure the leaf rust artificial epidemic inoculum was distributed evenly. The plots were protected from weeds and insect pests with agrochemicals applied as necessary. They were well managed with N, P, and K fertilization, and irrigated until all lines reached physiological maturity. Spreader rows and hill plots were inoculated with urediniospores of the leaf rust fungus race CBG/BP on 20 January 2015. Inoculation was repeated thrice to assure the onset of the epidemic. Adult plant leaf rust severity and response to infection were recorded when the susceptible check plots of Atil C2001, planted every 100 rows, displayed approximately 80 to 100% leaf rust severity. The rust severity was based on the modified Cobb Scale [To accurately measure the response to the two most common durum leaf rust races—CBG/BP and BBG/BP—whose avirulence/virulence formula is described above, the 482 durum wheat lines were planted at two locations and inoculated with different races at each location. The 482 accessions were sown in the field in plots of paired rows 1 m long from 20 to 25 November 2014 at the Norman E. Borlaug Experimental Station (CENEB) located in the Yaqui Valley in Sonora, Mexico. The experiment was sown on raised beds spaced at 80 cm intervals. Spreader rows of the susceptible variety ‘Storlom’ wheat . Adult plant leaf rust severity and response to infection were recorded when the susceptible check plots of Atil C2001 planted every 100 rows displayed approximately 80 to 100% leaf rust severity. The severity estimation was based on the modified Cobb Scale [A second field test was planted at the CIMMYT headquarters El Batan research station near Mexico City from 15 to 25 May. The spreader rows were a mixture of the durum cultivars Jupare C2001 and Banamichi C2004, which both carry In both field experiments, plant height, days to heading, grain color, growth habit, and the presence of leaf tip necrosis (LTN), were recorded. T. diccocum, and T. dicoccoides. The sources of resistance to leaf rust here identified at the seedling and adult stages can be combined to obtain higher levels of resistance and to assure not only the diversity, but to increase the number of resistant factors in improved genotypes, which in time will confer higher and stable resistance across environments. Several resistant sources identified in the present study are already incorporated in durum lines by the durum wheat breeding program at CIMMYT, which in the short term will enhance the gene pool diversity against P. triticina E. the causal agent of the wheat leaf rust.In the present study, high levels of diversity for leaf rust and other agronomic attributes were found among the core subset of durum landraces and pre-breeding lines from the CIMMYT durum wheat collection. High levels of resistance to durum wheat leaf rust identified at the seedling and adult stages suggest that there is enough variation in the collection, and that in the short term, it is not necessary to look farther into the secondary gene pool for resistance, other than into the tetraploid closest relatives such as Small seed samples of all accessions are available upon request to the first author or through CIMMYT .


Formative assessment (FA) is becoming increasingly common in higher education, although the teaching practice of student-centred FA in medical curricula is still very limited. In addition, there is a lack of theoretical and pedagogical practice studies observing FA from medical students’ perspectives. The aim of this study is to explore and understand ways to improve student-centred FA, and to provide a practical framework for the future construction of an FA index system in medical curricula.This study used questionnaire data from undergraduate students in clinical medicine, preventive medicine, radiology, and nursing at a comprehensive university in China. The feelings of medical students upon receiving student-centred FA, assessment of faculty feedback, and satisfaction were analysed descriptively.Of the 924 medical students surveyed, 37.1% had a general understanding of FA, 94.2% believed that the subject of teaching assessment was the teacher, 59% believed that teacher feedback on learning tasks was effective, and 36.3% received teacher feedback on learning tasks within one week. In addition, student satisfaction results show that students’ satisfaction with teacher feedback was 1.71 ± 0.747 points, and their satisfaction with learning tasks was 1.83 ± 0.826 points.Students as participants and collaborators in FA provide valid feedback for improving student-centred FA in terms of student cognition, empowered participation, and humanism. In addition, we suggest that medical educators avoid taking student satisfaction as a single indicator for measuring student-centred FA and to try to build an assessment index system of FA, to highlight the advantages of FA in medical curricula.The online version contains supplementary material available at 10.1186/s12909-023-04110-w. During the COVID-19 pandemic, teaching models, assessments and feedback mechanisms in medical curricula were forced to adapt and make changes to minimize the negative impact of the epidemic on medical education . AlthougStudent-centred includes a conceptual framework of three dimensions, namely cognitive (focus on student learning progress), agency (focus on student empowerment), and humanist  , 15, whiFormative assessment (FA) refers to the assessment in teachers and students systematically obtain evidence of students’ learning in the teaching process, promote students’ understanding of learning objectives, and support students to become learners and achieve learning objectives –23. TeacStudent satisfaction refers to the “subjective experience” of students in education and the perceived value of the learning experience , 32. GuiHence, this study selects medical students from a comprehensive university in China that has carried out medical curricula reform to observe and reflect on the content, methods, and feedback of teaching and learning assessments in medical curriculum through student-centred FA teaching practices. Based on the feedback regarding student satisfaction, we will also explore the shortcomings of FA as an indicator of student satisfaction and provide the best theoretical and practical framework for the design and implementation of FA in medicine or other disciplines.The FA of medical curricula in a comprehensive university in China follows the principle of “teaching-assessment-feedback”. Starting from the feedback on teaching objectives, it investigates students’ views on the implementation of FA, matches with knowledge objectives, ability objectives and emotional value objectives, analyses whether the teaching objectives have been achieved, and teachers immediately give feedback their opinions to students. FA methods include topic discussion, classroom questions, and answers, classroom tests, reflection logs, mind maps, etc., focusing on quantification. Each assessment module has a different emphasis on the training of medical students’ knowledge and ability. Evaluators’ assessment methods include: mutual assessment between teachers and students, mutual assessment between students and students, and self-assessment by students and teacher assessment. The total score of each medical course is generally composed of the weighted and cumulative scores of each module of formative assessment, plus the final exam scores. Based on clinical medicine, FA has been extended horizontally to nursing, public health and preventive medicine and other specialties. It extends vertically from undergraduate education to postgraduate education.In addition, the medical curriculum reform of this comprehensive university is student-centered, exploring the construction of a scientific and feasible FA index system, effectively evaluating teaching evaluation practices, and guiding teachers to cultivate students’ ability to reflect and learn independently. Therefore, from the perspective of students’ understanding, attitude and satisfaction to FA, enriching FA index system is worth discussing extensively.The study was designed as an investigative study. This comprehensive university in China have School of Clinical Medicine, School of Public Health, and School of Nursing. The undergraduate majors include clinical medicine, preventive medicine, radiology, and nursing. According to the research purpose, the research team has set the inclusion criteria for research objects, as follows: (1) undergraduate students receiving medical education, (2) undergraduate students who understand the research purpose; (3) undergraduate students who were voluntary to participate. Undergraduate students who did not receive medical course education, as well as undergraduate students who are conducting clinical practice, are excluded. The research team learned about the curriculum plan for the autumn semester of the academic year 2021–2022 in advance, and selected undergraduates majoring in clinical medicine, preventive medicine, radiology, and nursing from October 2021 to December 2021 in a comprehensive university in China for investigation.The research team contacted instructors of medical curricula who distributed questionnaires in class through an online questionnaire platform (Questionnaire Star), and members of the research team answered the questions raised by the students when filling in the questionnaire. The completion of the questionnaire was voluntary for the students and informed consent was obtained from all participants. The study was approved by the ethics committee of the college where the research team leading member was based .P < 0.001, indicating the reliability and validity of the questionnaire are good. The questionnaire is listed in the Supporting materials 1.The compilation of the questionnaire takes the student-centred conceptual framework of three dimensions as the theoretical basis of the research. In combination with the implementation background of FA in China’s medical education , 37, theStatistical analysis was performed using SPSS 26.0, and all statistical tests were two-sided, with P < 0.05 considered statistically significant. Data descriptions of medical students’ demographic information, medical students’ cognition of FA, feedback were expressed as frequencies and percentages. The results of student satisfaction were analysed and expressed as Mean ± Standard Deviation. For the word frequency in the answer text of the open question, Excel was used to make a word cloud to analysis.In our study, there were 984 questionnaires distributed, 924 valid questionnaires were collected, and the efficiency was 93.9%. Of the 924 participants, 290 were male (31.4%), 634 were female (68.6%), fresh man was 302 (32.7%), sophomore was 295 (31.9%), junior was 210 (22.7%) and senior was 117 (12.7%). Clinical medicine 238 (25.8%), preventive medicine 240 (26.0%), radiation medicine 200 (21.6%) and nursing 246 (26.6%).Students’ understanding of FA may help them participate in FA design, implementation and feedback. Before in-depth investigation, it is necessary to know the medical students’ understanding of FA. We through the question “How much do you know about formative assessment?”, preliminary understanding of medical students’ understanding of FA. Among the surveyed students, there were 143 (15.5%) very familiar, 205 (22.2%) understood, 343 (37.1%) general understood, 189 (20.5%) not very familiar, and 44 (4.8%) no familiar.  within one week, 275 (29.8%) immediately, 112 (12.1%) at the end of the course, 98 (10.6%) the second day, 52 (5.6%) within one month and 52 (5.6%) no feedback  thought it was the teacher, 45.1% (417/924) thought it was the student, 34.4% (318/924) thought it was peer, and 30.0% (277/924) thought it was a group (Fig. Open question “What formative assessment modules do you want to add in the future courses?“, The answer text is made into a word cloud, showing that the FA modules added by medical students in the future mainly include: peer assessment, presentation, questioning, take attendance, MOOC, etc. Fig. .The results of medical students’ satisfaction with various items of FA can reflect students’ acceptance of FA. The higher the satisfaction of medical students, they may have better learning effect. When they have better learning effect, they will also have higher degree of satisfaction, so as to achieve the purpose of FA implementation. The satisfaction of medical students reflects the implementation effect of FA in terms of FA method, content, tools informationization, scoring criteria, teacher feedback, and learning tasks. In the investigation, we found that more than 40% of the students think they are very satisfied with the method, content, tools informationization, scoring criteria, teacher feedback, and learning tasks in medical curricula FA, the results of student satisfaction show that students’ satisfaction with teacher feedback was 1.71 ± 0.747 points. Their satisfaction with learning tasks was 1.83 ± 0.826 points Table .To the best of our knowledge, this study was the first to survey undergraduate students covering clinical medicine, preventive medicine, public health, and nursing at a comprehensive Chinese university to analyse their perceptions, feedback, and satisfaction with implementation of student-centred FA in the medical curriculum. The results of this study indicate the necessity of medical students as subjects of FA, highlighting the concept of student-centred in three aspects: student cognition, empowered participation, and humanism. Of note is the value of student satisfaction as a measure of FA indicators.Medical students have lower degree of understanding of FA, which hinders the efficiency and effectiveness of FA feedback. The survey results showed that 37.1% had a general understanding of FA, even though the instructor introduced students to the scoring of each task in the FA design during the first session of each course. In addition, only 45.2% of medical students clearly understood how each section of the FA was scored. This differs from the results of the FA methodology survey conducted with teachers, who were very clear about the methodology and purpose of FA , 23, whiThe power-sharing of student-centred FA, with teachers playing the roles of organizers, managers, and collaborators, attempts to encourage students to shift from passive acceptance of assessment to active participation in assessment and to guide students to become the subjects of FA , 42. In Within the framework of student-centred theory, humanism focuses on understanding students’ aspirations, interests, and personalities and responding to them. The results of medical students’ satisfaction with each entry of FA in the survey showed that the mean score of the number of learning tasks reflected a low level of satisfaction, which is consistent with the results of previous FA satisfaction surveys , 45. It Our study has several limitations that we recommend that future studies consider and address. First, we analyse medical students’ perspectives on the implementing of FA in the medical course, but this does not represent the perspectives of students in other disciplines. The medical course has the educational goal of developing medical personnel with professional, clinical competence and a strong sense of empathy, which is somewhat different from the educational goals of other disciplines, and future replication in other fields is needed to be able to generalize these findings. Second, the survey was completed voluntarily by students. Although the 93.9% response rate was reasonable, the lack of effective participation by some medical students did introduce a selection bias that should be considered a potential limitation. Finally, this study was cross-sectional, conducted during an epidemic, lacking in-depth follow-up, and lacking consideration of whether students’ perspectives have changed as the FA progressed, focusing on medical students’ overall competency over a more extended time and their updated recommendations for the FA.With the wide application of FA, students’ views and attitudes towards this kind of teaching assessment are becoming increasingly important. We identified the important value of students as participants and collaborators in FA. In addition, combined with student satisfaction, we suggest that medical educators avoid using student satisfaction as a single indicator to measure the teaching effectiveness of student-centred FA. In the future, they might also incorporate diverse assessment indicators to construct an assessment index system for FA to highlight the advantages of FA in medical curricula.Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2Supplementary Material 3Supplementary Material 4Supplementary Material 5


To describe the urinary tract characteristics of diabetes insipidus (DI) patients with upper urinary tract dilatation (UUTD) using the video-urodynamic recordings (VUDS), UUTD and all urinary tract dysfunction (AUTD) systems, and to summarize the experience in the treatment of DI with UUTD.This retrospective study analyzed clinical data from 26 patients with DI, including micturition diary, water deprivation tests, imaging data and management. The UUTD and AUTD systems were used to evaluate the urinary tract characteristics. All patients were required to undergo VUDS, neurophysiologic tests to confirm the presence of neurogenic bladder (NB).2O in DI patients, and 42.3% (11/26) had a post-void residual >100 ml. NB was present in 6 (23.1%) of 26 DI patients with UUTD, and enterocystoplasty was recommended for two patients with poor bladder capacity, compliance and renal impairment. For the 24 remaining patients, medication combined with individualized and appropriate bladder management, including intermittent catheterization, indwelling catheter and regular voiding, achieved satisfactory results. High serum creatinine decreased from 248.0 ± 115.8 μmoI/L to 177.4 ± 92.8 μmoI/L in 12 patients from a population with a median of 108.1 μmoI/L (IQR: 79.9-206.5 μmoI/L). Forty-four dilated ureters showed significant improvement in the UUTD grade, and the median grade of 52 UUTD ureters decreased from 3 to 2.VUDS showed that the mean values for bladder capacity and bladder compliance were 575.0 ± 135.1 ml and 51.5 ± 33.6 cmHBladder distension, trabeculation and decreased or absent sensations were common features for DI patients with UUTD. Individualized therapy by medication combined with appropriate bladder management can improve UUTD and renal function in DI patients. This syLittle is known about the association between DI and urologic complications, bilateral upper urinary tract dilation (UUTD), and severe hydronephrosis without obstruction . PatientMost studies focusing on DI with hydroureteronephrosis have only been reported in the form of case reports, thus a systematic analysis of clinical characteristics and treatments for DI with UUTD are lacking. Another problem is the lack of a quantitative evaluation of the overall dilation, including hydronephrosis and ureteral dilation, from a coronal and transverse panel magnetic resonance urography (MRU) or 360-degree rotation. Hence, the purpose of this study was to summarize clinical characteristics, assessment, diagnosis, and treatments of patients with DI and UUTD to help urologists better understand this disease and improve the therapeutic effect of DI with UUTD.With the Ethics Committee of the China Rehabilitation Research Centre (No.2021-092-1) approval, we retrospectively reviewed the medical records of 26 patients diagnosed DI with hydroureteronephrosis at our center from January 2010. All of the patients provided a detailed history, physical examination, laboratory testing, the water deprivation test, magnetic resonance imaging (MRI) of the brain, ultrasound of the uropoietic system, MRU, radioactive nephrography, and video-urodynamics (VUDS) before treatment. Moreover, a neurologic examination and neurophysiologic testing were performed in patients with suspected DI and NB Figure 1The diagnostic criteria for DI are as follows , 6: (1) The micturition diary, a relatively objective detection method, has the advantages of non-invasiveness and repeatability. Moreover, it can identify whether frequent micturition is caused by an increase in absolute urine volume or just the increase in frequency.The water deprivation test and desamino-D-arginine vasopressin (DDAVP) test, when performed by an experienced physician are helpful to distinguish CDI, NDI, and PP Table S1Sellar tumors, craniocerebral surgery, and craniocerebral trauma account for 17% - 28%, 8% - 49%, and 2% - 11% of all causes of CDI, respectively . MultiplThe new UUTD and all urinary tract dysfunction (AUTD) grading system, established by Liao, is divided into 5 grades according to the MRU coronal and transverse image panels, and the maximum intensity projection MRU , 12. UUTLower urinary tract changes were evaluated using VUDS to assess bladder function. VUDS, consisting of cystometry and simultaneous cystography, was performed on patients based on the International Continence Society (ICS) standards .In a subset of patients with DI, abnormal urodynamics is similar to patients with NB, and neurophysiologic tests are effective ways to diagnose NB. These tests involving sacral reflex, somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) provide additional evidence in the search for neurogenic causes .All patients were classified as CDI or NDI. DDAVP is the primary treatment option for CDI. Unlike CDI treatment, NDI is treated with thiazide diuretics to reduce delivery of the filtrate to nephrons. Based on the VUDS, MRU, and uro-neurophysiologic evaluation, two patients underwent augmentation cystoplasty (AC) due to poor bladder capacity and compliance caused by a NB. Eight patients utilized the intermittent catheterization (IC) regimen for adequate bladder drainage due to detrusor underactivity or acontractile detrusor. Three patients preferred an indwelling catheter over intermittent catheterization to relieve urinary pressure and dilation. The remaining patients were treated with oral medications and a regular self-voiding regimen to alleviate polyuria and UUTD. The DDAVP combined with alpha blocker approach was used for two patients with dysuria and a small PVR. The various therapeutic regimens are summarized in t-test or the Wilcoxon signed rank test for quantitative variables. Statistical significance was defined as a P < 0.05.SPSS  was used for statistical analyses. Continuous variables are expressed as the mean ± SD or median (IQR). Frequency (percentage) was used to describe the count data. Differences between groups were assessed with Student’s There were 26 patients  with the main characteristics of DI who presented enuresis, dysuria and UUTD, of whom 6 were diagnosed with DI accompanied with NB. The etiology of NB, including spinal cord injury, spina bifida, and diabetes mellitus, was established through a detailed history and imaging findings in patients with NB, and further confirmed by neurophysiologic tests. 23 (88.5%) had CDI and 3 (11.5%) had NDI, and median duration of DI was 10.0 years (IQR: 4.3-24.3 years). The demographic and baseline characteristics of the primary assessment are listed in 2O during the stable filling period. The median PVR and maximum flow rate was 30.0 ml (IQR: 0-302.5 ml) and 20.8 ± 12.1 ml/s in all patients, respectively, and 42.3% of patients (11/26) had a PVR >100 ml (355.5 ± 190.0 ml) due to incomplete bladder emptying.According to the AUTD system, the features of the lower urinary tract in DI patients with UUTD is in Clinical follow-up period ranged from 1 to 12 months. The differences in pre- and post-therapeutic parameters for DI patients are shown in Ultrasonography showed that there was obvious separation of the central renal complex and dilatation of the ureter in all patients. The separations of the central renal complex for two kidneys improved with proper treatment . Indeed, a comprehensive MRU evaluation based on the UUTD and AUTD systems revealed that all patients had bilateral dilations of the pelvis and ureters before treatment Figure 3DI, a common disorder with an inability to conserve water and concentrate the urine, frequently results in polydipsia, polyuria, and electrolyte abnormalities , 15.Bladder distension and UUTD are considered rare complications of DI, and prolonged polyuria plays an important role in bilateral, non-obstructive UUTD, which has been reported in patients with DI , 16. In These above-mentioned characteristics are reflected in urodynamics, which usually present with a high-capacity, compliant bladder and decreased or absent bladder sensations. Our results showed decreased or absent bladder sensations in 17 patients. Furthermore, the investigation of VUDS showed diminished detrusor contractility and a hypertrophic bladder for most DI patients with UUTD . UltrasoUrinary symptoms and imaging findings of most DI patients with UUTD were similar to patients with NB, presenting with urinary frequency, enuresis, dysuria, varying degrees of UUTD, and bladder trabeculation. Nevertheless, many urologists are unfamiliar with this condition and might confuse DI with NB . In this2O), UUTD (grade≥ III) and renal function dysfunction (Scr≥1.5mg/dL) caused by NB, who achieved satisfactory outcomes. Therefore, we are of the opinion that AC is a feasible option to alleviate progressive renal decline for patients with worsening compliance and deteriorating renal function. In our study, a subset of patients with detrusor contraction but dysuria self-voided with a combination of α-blockers. We managed all patients with individualized treatments to alleviate UUTD and renal deterioration and improve independence and QoL.Polyuria is one of the major components of urinary dilatation and renal function failure. Hence, reducing the urine volume and the PVR are critical approaches in the management of DI patients with UUTD . TreatmeAt present, there is no evidence on how long DI will develop into hydronephrosis or whether it can be reversed ; howeverOur study had some limitations, including the retrospective design and the small number of patients. In addition, although a summary of our experience can help urologists understand DI with UUTD, the current study was limited by the short follow-up time. Furthermore, because of the limited sample size, further multicenter, clinical trials with a larger sample size are required.In conclusion, DI should be considered in patients with polydipsia, polyuria, and urinary tract dilation. Bladder distension, trabeculation, decreased or absent bladder sensations and contractility were common features for DI patients with UUTD Urologists should pay attention to the similarity of symptoms between DI with UUTD and NB, physical and neurological examination, VUDS, neurophysiologic tests were recommended for DI patients with UUTD to differentiate between DI and NB. In DI patients with UUTD, pharmacological treatments reducing fluid intake and urine volume combined with appropriate bladder management can improve UUTD and renal function in DI patients.The original contributions presented in the study are included in the article/This study protocol was in accordance with the ethical code of the 1975 Declaration of Helsinki and was approved by the Ethics Committee of the China Rehabilitation Research Centre (No.2021-092-1).LL: Project development, Data management, Study coordination. XW: Data management and analysis, Manuscript writing. XY: Data management and analysis. FZ, XL and GC: Data management. ZZ: Data analysis. All authors contributed to the article and approved the submitted version.This study was supported by grants from the National Natural Science Foundation of China (No: 81870523).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.